chr8-119732053-C-T

Position:

chr8-119732053-C-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The ENST00000378164.7(TAF2):c.3471G>A(p.Lys1157=) variant causes a synonymous change. The variant allele was found at a frequency of 0.0192 in 1,614,052 control chromosomes in the GnomAD database, including 387 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 31 hom., cov: 32)

Exomes 𝑓: 0.020 ( 356 hom. )

Consequence

TAF2
ENST00000378164.7 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 6.30

Variant links:

Genes affected

TAF2 (HGNC:11536): (TATA-box binding protein associated factor 2) Initiation of transcription by RNA polymerase II requires the activities of more than 70 polypeptides. The protein that coordinates these activities is transcription factor IID (TFIID), which binds to the core promoter to position the polymerase properly, serves as the scaffold for assembly of the remainder of the transcription complex, and acts as a channel for regulatory signals. TFIID is composed of the TATA-binding protein (TBP) and a group of evolutionarily conserved proteins known as TBP-associated factors or TAFs. TAFs may participate in basal transcription, serve as coactivators, function in promoter recognition or modify general transcription factors (GTFs) to facilitate complex assembly and transcription initiation. This gene encodes one of the larger subunits of TFIID that is stably associated with the TFIID complex. It contributes to interactions at and downstream of the transcription initiation site, interactions that help determine transcription complex response to activators. [provided by RefSeq, Jul 2008]

TAF2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.22).

BP6

Variant 8-119732053-C-T is Benign according to our data. Variant chr8-119732053-C-T is described in ClinVar as [Benign]. Clinvar id is 1169029.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0157 (2384/152242) while in subpopulation NFE AF= 0.0228 (1548/68020). AF 95% confidence interval is 0.0218. There are 31 homozygotes in gnomad4. There are 1142 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 31 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAF2	NM_003184.4 linkuse as main transcript	c.3471G>A	p.Lys1157=	synonymous_variant	26/26	ENST00000378164.7	NP_003175.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAF2	ENST00000378164.7 linkuse as main transcript	c.3471G>A	p.Lys1157=	synonymous_variant	26/26	1	NM_003184.4	ENSP00000367406	P1

Frequencies

GnomAD3 genomes

AF:

0.0157

AC:

2383

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00389

Gnomad AMI

AF:

0.0592

Gnomad AMR

AF:

0.0126

Gnomad ASJ

AF:

0.0533

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.0188

Gnomad MID

AF:

0.0191

Gnomad NFE

AF:

0.0228

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.0165

AC:

4158

AN:

251322

Hom.:

AF XY:

0.0164

AC XY:

2227

AN XY:

135820

show subpopulations

Gnomad AFR exome

AF:

0.00394

Gnomad AMR exome

AF:

0.00746

Gnomad ASJ exome

AF:

0.0568

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00310

Gnomad FIN exome

AF:

0.0187

Gnomad NFE exome

AF:

0.0234

Gnomad OTH exome

AF:

0.0179

GnomAD4 exome

AF:

0.0196

AC:

28598

AN:

1461810

Hom.:

356

Cov.:

AF XY:

0.0191

AC XY:

13905

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.00361

Gnomad4 AMR exome

AF:

0.00756

Gnomad4 ASJ exome

AF:

0.0582

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00294

Gnomad4 FIN exome

AF:

0.0183

Gnomad4 NFE exome

AF:

0.0216

Gnomad4 OTH exome

AF:

0.0196

GnomAD4 genome

AF:

0.0157

AC:

2384

AN:

152242

Hom.:

Cov.:

AF XY:

0.0153

AC XY:

1142

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.00388

Gnomad4 AMR

AF:

0.0126

Gnomad4 ASJ

AF:

0.0533

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00270

Gnomad4 FIN

AF:

0.0188

Gnomad4 NFE

AF:

0.0228

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.0227

Hom.:

Bravo

AF:

0.0146

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.0237

EpiControl

AF:

0.0255

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	Jan 30, 2024	- -

Microcephaly-thin corpus callosum-intellectual disability syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Molecular Genetics, Royal Melbourne Hospital

May 04, 2023

European Non-Finnish population allele frequency is 2.261% (rs61753747, 2998/129026 alleles, 39 homozygotes in gnomAD v2.1). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.2.1, this variant is classified as BENIGN. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.22

CADD

Benign

9.2

DANN

Benign

0.74

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

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