dbSNP rs2492937: TAF8:c.921-111G>A (chr6-42086608-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000456846.6(TAF8):c.921-111G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 1,063,322 control chromosomes in the GnomAD database, including 26,731 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.28 ( 8968 hom., cov: 32)

Exomes 𝑓: 0.18 ( 17763 hom. )

Consequence

TAF8
ENST00000456846.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.137

Publications

3 publications found

Variant links:

Genes affected

TAF8 (HGNC:17300): (TATA-box binding protein associated factor 8) This gene encodes one of several TATA-binding protein (TBP)-associated factors (TAFs), which are integral subunits of the general transcription factor complex TFIID. TFIID recognizes the core promoter of many genes and nucleates the assembly of a transcription preinitiation complex containing RNA polymerase II and other initiation factors. The protein encoded by this gene contains an H4-like histone fold domain, and interacts with several subunits of TFIID including TBP and the histone-fold protein TAF10. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

TAF8 Gene-Disease associations (from GenCC):

neurodevelopmental disorder with severe motor impairment, absent language, cerebral hypomyelination, and brain atrophy
Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

TAF8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
TAF8	NM_001438580.1 link	c.*26-111G>A	intron_variant	Intron 9 of 9	NP_001425509.1
TAF8	NM_001410907.1 link	c.921-111G>A	intron_variant	Intron 8 of 8	NP_001397836.1
TAF8	NM_001438582.1 link	c.630-111G>A	intron_variant	Intron 6 of 6	NP_001425511.1
TAF8	XM_047418177.1 link	c.*26-111G>A	intron_variant	Intron 9 of 9	XP_047274133.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAF8	ENST00000456846.6 link	c.921-111G>A		intron_variant	Intron 8 of 8	1		ENSP00000411900.2
TAF8	ENST00000372982.8 link	c.*26-111G>A		intron_variant	Intron 9 of 9	2		ENSP00000362073.4

Frequencies

GnomAD3 genomes

AF:

0.281

AC:

42732

AN:

151938

Hom.:

8940

Cov.:

show subpopulations

Gnomad AFR

AF:

0.595

Gnomad AMI

AF:

0.189

Gnomad AMR

AF:

0.155

Gnomad ASJ

AF:

0.186

Gnomad EAS

AF:

0.0929

Gnomad SAS

AF:

0.122

Gnomad FIN

AF:

0.132

Gnomad MID

AF:

0.201

Gnomad NFE

AF:

0.175

Gnomad OTH

AF:

0.251

GnomAD4 exome

AF:

0.181

AC:

165286

AN:

911266

Hom.:

17763

AF XY:

0.178

AC XY:

83626

AN XY:

468924

show subpopulations

African (AFR)

AF:

0.618

AC:

13632

AN:

22060

American (AMR)

AF:

0.111

AC:

3877

AN:

35038

Ashkenazi Jewish (ASJ)

AF:

0.188

AC:

4158

AN:

22098

East Asian (EAS)

AF:

0.104

AC:

3484

AN:

33490

South Asian (SAS)

AF:

0.138

AC:

9582

AN:

69292

European-Finnish (FIN)

AF:

0.143

AC:

6825

AN:

47856

Middle Eastern (MID)

AF:

0.182

AC:

867

AN:

4772

European-Non Finnish (NFE)

AF:

0.180

AC:

114417

AN:

634516

Other (OTH)

AF:

0.200

AC:

8444

AN:

42144

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

6710

13420

20130

26840

33550

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3170

6340

9510

12680

15850

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.282

AC:

42808

AN:

152056

Hom.:

8968

Cov.:

AF XY:

0.274

AC XY:

20355

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.595

AC:

24657

AN:

41448

American (AMR)

AF:

0.154

AC:

2361

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.186

AC:

644

AN:

3468

East Asian (EAS)

AF:

0.0927

AC:

479

AN:

5166

South Asian (SAS)

AF:

0.122

AC:

591

AN:

4826

European-Finnish (FIN)

AF:

0.132

AC:

1397

AN:

10594

Middle Eastern (MID)

AF:

0.199

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.175

AC:

11925

AN:

67960

Other (OTH)

AF:

0.249

AC:

524

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1270

2540

3810

5080

6350

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

392

784

1176

1568

1960

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.217

Hom.:

13552

Bravo

AF:

0.299

Asia WGS

AF:

0.121

AC:

423

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.9

(source)

DANN

Benign

0.63

PhyloP100

-0.14

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over