Genetic Variant ENST00000456846.6: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

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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