7-92528821-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_032120.4(RBM48):c.8C>T(p.Ser3Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00135 in 1,613,860 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0074 ( 16 hom., cov: 32)

Exomes 𝑓: 0.00073 ( 12 hom. )

Consequence

RBM48
NM_032120.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.227

Publications

3 publications found

Variant links:

Genes affected

RBM48 (HGNC:21785): (RNA binding motif protein 48) Predicted to enable RNA binding activity. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

RBM48 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0042303503).

BP6

Variant 7-92528821-C-T is Benign according to our data. Variant chr7-92528821-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 776237.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00736 (1121/152288) while in subpopulation AFR AF = 0.0256 (1064/41546). AF 95% confidence interval is 0.0243. There are 16 homozygotes in GnomAd4. There are 530 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM48	NM_032120.4 link	c.8C>T	p.Ser3Leu	missense_variant	Exon 1 of 5	ENST00000265732.10	NP_115496.2	Q5RL73-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RBM48	ENST00000265732.10 link	c.8C>T	p.Ser3Leu	missense_variant	Exon 1 of 5	1	NM_032120.4	ENSP00000265732.5	Q5RL73-1
RBM48	ENST00000481551.5 link	c.8C>T	p.Ser3Leu	missense_variant	Exon 1 of 4	1		ENSP00000419242.1	Q5RL73-2
RBM48	ENST00000496410.1 link	c.-426C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 3	3		ENSP00000418333.1	C9J787
RBM48	ENST00000496410.1 link	c.-426C>T		5_prime_UTR_variant	Exon 1 of 3	3		ENSP00000418333.1	C9J787

Frequencies

GnomAD3 genomes

AF:

0.00733

AC:

1115

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0255

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00255

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00765

GnomAD2 exomes

AF:

0.00173

AC:

431

AN:

248726

AF XY:

0.00126

show subpopulations

Gnomad AFR exome

AF:

0.0251

Gnomad AMR exome

AF:

0.00113

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000355

Gnomad OTH exome

AF:

0.000332

GnomAD4 exome

AF:

0.000726

AC:

1061

AN:

1461572

Hom.:

Cov.:

AF XY:

0.000593

AC XY:

431

AN XY:

727074

show subpopulations

African (AFR)

AF:

0.0264

AC:

882

AN:

33464

American (AMR)

AF:

0.00123

AC:

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86218

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000153

AC:

AN:

1111802

Other (OTH)

AF:

0.00176

AC:

106

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

104

157

209

261

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00736

AC:

1121

AN:

152288

Hom.:

Cov.:

AF XY:

0.00712

AC XY:

530

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.0256

AC:

1064

AN:

41546

American (AMR)

AF:

0.00255

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68022

Other (OTH)

AF:

0.00757

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

113

170

226

283

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00277

Hom.:

Bravo

AF:

0.00836

ESP6500AA

AF:

0.0239

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00209

AC:

252

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Sep 11, 2018

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 02, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.048

T;.

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.77

T;T

MetaRNN

Benign

0.0042

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

L;L

PhyloP100

0.23

PrimateAI

Benign

0.40

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.027

Sift

Benign

0.030

D;D

Sift4G

Benign

0.090

T;T

Polyphen

0.14

B;.

Vest4

0.13

MVP

0.74

MPC

0.19

ClinPred

0.054

GERP RS

2.8

PromoterAI

-0.19

Neutral

(source)

Varity_R

0.11

gMVP

0.61

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

7-92528821-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over