Variant 7-75056083-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000610322.5(RCC1L):c.1058-9G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 1,613,560 control chromosomes in the GnomAD database, including 15,271 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1113 hom., cov: 32)

Exomes 𝑓: 0.13 ( 14158 hom. )

Consequence

RCC1L
ENST00000610322.5 intron

Scores

Splicing: ADA: 0.0002131

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.983

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:

RCC1L (HGNC:):

RCC1L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 7-75056083-C-A is Benign according to our data. Variant chr7-75056083-C-A is described in ClinVar as [Benign]. Clinvar id is 770938.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
RCC1L	NM_030798.5 linkuse as main transcript	c.1058-9G>T	intron_variant	ENST00000610322.5	NP_110425.2	Q96I51-1
RCC1L	NM_148842.3 linkuse as main transcript	c.1058-9G>T	intron_variant		NP_683682.1	Q96I51-3
RCC1L	NM_001363447.2 linkuse as main transcript	c.659-9G>T	intron_variant		NP_001350376.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
RCC1L	ENST00000610322.5 linkuse as main transcript	c.1058-9G>T	intron_variant	1	NM_030798.5	ENSP00000480364.1	Q96I51-1
RCC1L	ENST00000614461.4 linkuse as main transcript	c.1058-9G>T	intron_variant	1		ENSP00000477659.1	Q96I51-3
RCC1L	ENST00000616051.1 linkuse as main transcript	n.1111-9G>T	intron_variant	2
RCC1L	ENST00000618102.4 linkuse as main transcript	n.555-9G>T	intron_variant	2

Frequencies

GnomAD3 genomes

AF:

0.112

AC:

17058

AN:

152046

Hom.:

1113

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0577

Gnomad AMI

AF:

0.0800

Gnomad AMR

AF:

0.129

Gnomad ASJ

AF:

0.152

Gnomad EAS

AF:

0.00636

Gnomad SAS

AF:

0.0875

Gnomad FIN

AF:

0.0982

Gnomad MID

AF:

0.288

Gnomad NFE

AF:

0.151

Gnomad OTH

AF:

0.130

GnomAD3 exomes

AF:

0.112

AC:

22670

AN:

203246

Hom.:

1503

AF XY:

0.115

AC XY:

12720

AN XY:

110886

show subpopulations

Gnomad AFR exome

AF:

0.0602

Gnomad AMR exome

AF:

0.0840

Gnomad ASJ exome

AF:

0.162

Gnomad EAS exome

AF:

0.00518

Gnomad SAS exome

AF:

0.0971

Gnomad FIN exome

AF:

0.0913

Gnomad NFE exome

AF:

0.149

Gnomad OTH exome

AF:

0.145

GnomAD4 exome

AF:

0.135

AC:

197137

AN:

1461396

Hom.:

14158

Cov.:

AF XY:

0.135

AC XY:

98323

AN XY:

727014

show subpopulations

Gnomad4 AFR exome

AF:

0.0614

Gnomad4 AMR exome

AF:

0.0875

Gnomad4 ASJ exome

AF:

0.162

Gnomad4 EAS exome

AF:

0.00227

Gnomad4 SAS exome

AF:

0.0993

Gnomad4 FIN exome

AF:

0.0929

Gnomad4 NFE exome

AF:

0.147

Gnomad4 OTH exome

AF:

0.134

GnomAD4 genome

AF:

0.112

AC:

17079

AN:

152164

Hom.:

1113

Cov.:

AF XY:

0.109

AC XY:

8138

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.0580

Gnomad4 AMR

AF:

0.129

Gnomad4 ASJ

AF:

0.152

Gnomad4 EAS

AF:

0.00638

Gnomad4 SAS

AF:

0.0884

Gnomad4 FIN

AF:

0.0982

Gnomad4 NFE

AF:

0.151

Gnomad4 OTH

AF:

0.128

Alfa

AF:

0.101

Hom.:

278

Bravo

AF:

0.112

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00021

dbscSNV1_RF

Benign

0.024

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

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