Variant 16-74636560-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000361070.9(RFWD3):c.1212G>A(p.Thr404=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 1,611,680 control chromosomes in the GnomAD database, including 229,707 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 27489 hom., cov: 31)

Exomes 𝑓: 0.52 ( 202218 hom. )

Consequence

RFWD3
ENST00000361070.9 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.458

Variant links:

Genes affected

RFWD3 (HGNC:25539): (ring finger and WD repeat domain 3) Enables MDM2/MDM4 family protein binding activity; p53 binding activity; and ubiquitin protein ligase activity. Involved in several processes, including DNA metabolic process; regulation of cell cycle phase transition; and response to ionizing radiation. Located in nucleoplasm and site of DNA damage. Colocalizes with site of double-strand break. Implicated in Fanconi anemia. [provided by Alliance of Genome Resources, Apr 2022]

RFWD3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 16-74636560-C-T is Benign according to our data. Variant chr16-74636560-C-T is described in ClinVar as [Benign]. Clinvar id is 1327953.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.458 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.762 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RFWD3	NM_018124.4 linkuse as main transcript	c.1212G>A	p.Thr404=	synonymous_variant	8/13	ENST00000361070.9	NP_060594.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RFWD3	ENST00000361070.9 linkuse as main transcript	c.1212G>A	p.Thr404=	synonymous_variant	8/13	1	NM_018124.4	ENSP00000354361	P1
RFWD3	ENST00000571750.5 linkuse as main transcript	c.1212G>A	p.Thr404=	synonymous_variant	9/14	2		ENSP00000460049	P1

Frequencies

GnomAD3 genomes

AF:

0.588

AC:

89303

AN:

151882

Hom.:

27453

Cov.:

show subpopulations

Gnomad AFR

AF:

0.768

Gnomad AMI

AF:

0.562

Gnomad AMR

AF:

0.502

Gnomad ASJ

AF:

0.479

Gnomad EAS

AF:

0.753

Gnomad SAS

AF:

0.619

Gnomad FIN

AF:

0.456

Gnomad MID

AF:

0.544

Gnomad NFE

AF:

0.510

Gnomad OTH

AF:

0.588

GnomAD3 exomes

AF:

0.538

AC:

134863

AN:

250466

Hom.:

37850

AF XY:

0.540

AC XY:

73174

AN XY:

135414

show subpopulations

Gnomad AFR exome

AF:

0.773

Gnomad AMR exome

AF:

0.419

Gnomad ASJ exome

AF:

0.471

Gnomad EAS exome

AF:

0.756

Gnomad SAS exome

AF:

0.604

Gnomad FIN exome

AF:

0.447

Gnomad NFE exome

AF:

0.512

Gnomad OTH exome

AF:

0.528

GnomAD4 exome

AF:

0.521

AC:

760547

AN:

1459680

Hom.:

202218

Cov.:

AF XY:

0.523

AC XY:

379750

AN XY:

726126

show subpopulations

Gnomad4 AFR exome

AF:

0.776

Gnomad4 AMR exome

AF:

0.429

Gnomad4 ASJ exome

AF:

0.478

Gnomad4 EAS exome

AF:

0.747

Gnomad4 SAS exome

AF:

0.598

Gnomad4 FIN exome

AF:

0.445

Gnomad4 NFE exome

AF:

0.506

Gnomad4 OTH exome

AF:

0.545

GnomAD4 genome

AF:

0.588

AC:

89389

AN:

152000

Hom.:

27489

Cov.:

AF XY:

0.586

AC XY:

43560

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.769

Gnomad4 AMR

AF:

0.501

Gnomad4 ASJ

AF:

0.479

Gnomad4 EAS

AF:

0.753

Gnomad4 SAS

AF:

0.618

Gnomad4 FIN

AF:

0.456

Gnomad4 NFE

AF:

0.510

Gnomad4 OTH

AF:

0.588

Alfa

AF:

0.528

Hom.:

50404

Bravo

AF:

0.597

Asia WGS

AF:

0.695

AC:

2413

AN:

3478

EpiCase

AF:

0.507

EpiControl

AF:

0.521

ClinVar

Significance: Benign

Submissions summary: Benign:3

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	Feb 01, 2024	- -

Fanconi anemia, complementation group W

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

2.5

DANN

Benign

0.34

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