Variant 7-75073695-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_030798.5(RCC1L):c.43C>T(p.Arg15Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.014 in 1,506,886 control chromosomes in the GnomAD database, including 195 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0090 ( 13 hom., cov: 32)

Exomes 𝑓: 0.015 ( 182 hom. )

Consequence

RCC1L
NM_030798.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.282

Variant links:

Genes affected

RCC1L (HGNC:14948): (RCC1 like) This gene encodes a protein containing regulator of chromosome condensation 1-like repeats. The encoded protein may function as a guanine nucleotide exchange factor. This gene is located in a region of chromosome 7 that is deleted in Williams-Beuren syndrome, a multisystem developmental disorder. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

RCC1L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0059011877).

BP6

Variant 7-75073695-G-A is Benign according to our data. Variant chr7-75073695-G-A is described in ClinVar as [Benign]. Clinvar id is 2657607.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0145 (19671/1354730) while in subpopulation NFE AF= 0.0169 (18010/1066706). AF 95% confidence interval is 0.0167. There are 182 homozygotes in gnomad4_exome. There are 9553 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RCC1L	NM_030798.5 linkuse as main transcript	c.43C>T	p.Arg15Trp	missense_variant	1/11	ENST00000610322.5	NP_110425.2
RCC1L	NM_148842.3 linkuse as main transcript	c.43C>T	p.Arg15Trp	missense_variant	1/11		NP_683682.1
RCC1L	NM_001281441.2 linkuse as main transcript	c.43C>T	p.Arg15Trp	missense_variant	1/9		NP_001268370.1
RCC1L	NM_001363447.2 linkuse as main transcript	c.-591C>T		5_prime_UTR_variant	1/11		NP_001350376.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RCC1L	ENST00000610322.5 linkuse as main transcript	c.43C>T	p.Arg15Trp	missense_variant	1/11	1	NM_030798.5	ENSP00000480364	P1	Q96I51-1

Frequencies

GnomAD3 genomes

AF:

0.00896

AC:

1362

AN:

152048

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00333

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.00694

Gnomad ASJ

AF:

0.00577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00424

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0149

Gnomad OTH

AF:

0.00813

GnomAD3 exomes

AF:

0.00878

AC:

899

AN:

102430

Hom.:

AF XY:

0.00906

AC XY:

516

AN XY:

56956

show subpopulations

Gnomad AFR exome

AF:

0.00222

Gnomad AMR exome

AF:

0.00486

Gnomad ASJ exome

AF:

0.00497

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00556

Gnomad FIN exome

AF:

0.00472

Gnomad NFE exome

AF:

0.0160

Gnomad OTH exome

AF:

0.00836

GnomAD4 exome

AF:

0.0145

AC:

19671

AN:

1354730

Hom.:

182

Cov.:

AF XY:

0.0143

AC XY:

9553

AN XY:

667890

show subpopulations

Gnomad4 AFR exome

AF:

0.00216

Gnomad4 AMR exome

AF:

0.00592

Gnomad4 ASJ exome

AF:

0.00575

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00574

Gnomad4 FIN exome

AF:

0.00432

Gnomad4 NFE exome

AF:

0.0169

Gnomad4 OTH exome

AF:

0.0122

GnomAD4 genome

AF:

0.00895

AC:

1362

AN:

152156

Hom.:

Cov.:

AF XY:

0.00817

AC XY:

608

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.00332

Gnomad4 AMR

AF:

0.00694

Gnomad4 ASJ

AF:

0.00577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.00424

Gnomad4 NFE

AF:

0.0149

Gnomad4 OTH

AF:

0.00805

Alfa

AF:

0.00445

Hom.:

Bravo

AF:

0.00960

ExAC

AF:

0.00442

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2023

RCC1L: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.0082

MetaRNN

Benign

0.0059

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Pathogenic

0.84

Sift4G

Benign

0.14

T;T;T

Vest4

0.15

MVP

0.44

ClinPred

0.039

GERP RS

3.6

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

3.3

gMVP

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over