NM_032120.4:c.27G>A

Variant names:

• chr7-92528840-G-A
• rs117787377
• NM_032120.4:c.27G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_032120.4(RBM48):​c.27G>A​(p.Gly9Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0133 in 1,614,042 control chromosomes in the GnomAD database, including 183 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.010 (11 hom., cov: 32)
  • Exomes 𝑓: 0.014 (172 hom.)
• Consequence: RBM48 NM_032120.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.908
• Publications: 5 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 7-92528840-G-A is Benign according to our data. Variant chr7-92528840-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1211594.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.908 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0101 (1541/152312) while in subpopulation NFE AF = 0.0162 (1101/68024). AF 95% confidence interval is 0.0154. There are 11 homozygotes in GnomAd4. There are 677 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM48	NM_032120.4	c.27G>A	p.Gly9Gly	synonymous_variant	Exon 1 of 5	ENST00000265732.10	NP_115496.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM48	ENST00000265732.10	c.27G>A	p.Gly9Gly	synonymous_variant	Exon 1 of 5	1	NM_032120.4	ENSP00000265732.5
RBM48	ENST00000481551.5	c.27G>A	p.Gly9Gly	synonymous_variant	Exon 1 of 4	1		ENSP00000419242.1
RBM48	ENST00000496410.1	c.-407G>A		5_prime_UTR_variant	Exon 1 of 3	3		ENSP00000418333.1

Frequencies

GnomAD3 genomes AF: 0.0101 AC: 1540 AN: 152192 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.00299

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0104

Gnomad ASJ AF: 0.00749

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00393

Gnomad FIN AF: 0.00613

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0162

Gnomad OTH AF: 0.0105

GnomAD2 exomes AF: 0.0106 AC: 2626 AN: 248856 AF XY: 0.0105

Gnomad AFR exome AF: 0.00273

Gnomad AMR exome AF: 0.00757

Gnomad ASJ exome AF: 0.0124

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00693

Gnomad NFE exome AF: 0.0170

Gnomad OTH exome AF: 0.0142

GnomAD4 exome AF: 0.0136 AC: 19882 AN: 1461730 Hom.: 172 Cov.: 31 AF XY: 0.0133 AC XY: 9644 AN XY: 727168

African (AFR) AF: 0.00248 AC: 83 AN: 33474

American (AMR) AF: 0.00776 AC: 347 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0113 AC: 295 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00218 AC: 188 AN: 86240

European-Finnish (FIN) AF: 0.00766 AC: 409 AN: 53416

Middle Eastern (MID) AF: 0.0151 AC: 87 AN: 5768

European-Non Finnish (NFE) AF: 0.0160 AC: 17751 AN: 1111898

Other (OTH) AF: 0.0119 AC: 721 AN: 60378

GnomAD4 genome AF: 0.0101 AC: 1541 AN: 152312 Hom.: 11 Cov.: 32 AF XY: 0.00909 AC XY: 677 AN XY: 74480

African (AFR) AF: 0.00298 AC: 124 AN: 41572

American (AMR) AF: 0.0104 AC: 159 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00749 AC: 26 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00394 AC: 19 AN: 4826

European-Finnish (FIN) AF: 0.00613 AC: 65 AN: 10610

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0162 AC: 1101 AN: 68024

Other (OTH) AF: 0.0104 AC: 22 AN: 2116

Alfa AF: 0.0142 Hom.: 6

Bravo AF: 0.0103

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.0179

EpiControl AF: 0.0188

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Dec 02, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 29, 2018

GeneDx

Significance: Likely 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
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.30
DANN	Benign	0.86
PhyloP100		-0.91
PromoterAI		-0.0021	Neutral
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs117787377; hg19: chr7-92158154;