Variant chr1-92088726-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001376131.1(BTBD8):c.178G>A(p.Val60Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0246 in 1,610,170 control chromosomes in the GnomAD database, including 609 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.019 ( 40 hom., cov: 32)

Exomes 𝑓: 0.025 ( 569 hom. )

Consequence

BTBD8
NM_001376131.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.04

Variant links:

Genes affected

BTBD8 (HGNC:21019): (BTB domain containing 8) Predicted to be involved in clathrin-dependent synaptic vesicle endocytosis; neuron projection development; and synaptic vesicle budding from endosome. Located in nucleoplasm. Colocalizes with AP-2 adaptor complex. [provided by Alliance of Genome Resources, Apr 2022]

BTBD8 links:

BTBD8 (HGNC:):

BTBD8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005039811).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0193 (2935/152124) while in subpopulation NFE AF= 0.028 (1900/67974). AF 95% confidence interval is 0.0269. There are 40 homozygotes in gnomad4. There are 1432 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 40 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BTBD8	NM_001376131.1 linkuse as main transcript	c.178G>A	p.Val60Ile	missense_variant	2/18	ENST00000636805.2	NP_001363060.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
BTBD8	ENST00000636805.2 linkuse as main transcript	c.178G>A	p.Val60Ile	missense_variant	2/18	5	NM_001376131.1	ENSP00000490161.1	Q5XKL5-3
BTBD8	ENST00000342818.4 linkuse as main transcript	c.178G>A	p.Val60Ile	missense_variant	2/9	1		ENSP00000343686.3	A0A8V8N7F1
BTBD8	ENST00000370382.7 linkuse as main transcript	n.445G>A		non_coding_transcript_exon_variant	2/6	1
BTBD8	ENST00000635934.1 linkuse as main transcript	n.178G>A		non_coding_transcript_exon_variant	2/17	5		ENSP00000490386.1	B4DKD6

Frequencies

GnomAD3 genomes

AF:

0.0193

AC:

2936

AN:

152006

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00498

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.0189

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00353

Gnomad FIN

AF:

0.0439

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0280

Gnomad OTH

AF:

0.0187

GnomAD3 exomes

AF:

0.0202

AC:

5071

AN:

250480

Hom.:

AF XY:

0.0200

AC XY:

2707

AN XY:

135446

show subpopulations

Gnomad AFR exome

AF:

0.00363

Gnomad AMR exome

AF:

0.0104

Gnomad ASJ exome

AF:

0.00189

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00519

Gnomad FIN exome

AF:

0.0366

Gnomad NFE exome

AF:

0.0315

Gnomad OTH exome

AF:

0.0187

GnomAD4 exome

AF:

0.0252

AC:

36719

AN:

1458046

Hom.:

569

Cov.:

AF XY:

0.0243

AC XY:

17618

AN XY:

725354

show subpopulations

Gnomad4 AFR exome

AF:

0.00413

Gnomad4 AMR exome

AF:

0.0109

Gnomad4 ASJ exome

AF:

0.00238

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00588

Gnomad4 FIN exome

AF:

0.0357

Gnomad4 NFE exome

AF:

0.0292

Gnomad4 OTH exome

AF:

0.0196

GnomAD4 genome

AF:

0.0193

AC:

2935

AN:

152124

Hom.:

Cov.:

AF XY:

0.0193

AC XY:

1432

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.00496

Gnomad4 AMR

AF:

0.0189

Gnomad4 ASJ

AF:

0.00231

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00353

Gnomad4 FIN

AF:

0.0439

Gnomad4 NFE

AF:

0.0280

Gnomad4 OTH

AF:

0.0185

Alfa

AF:

0.0243

Hom.:

Bravo

AF:

0.0172

TwinsUK

AF:

0.0310

AC:

115

ALSPAC

AF:

0.0265

AC:

102

ESP6500AA

AF:

0.00590

AC:

ESP6500EA

AF:

0.0302

AC:

260

ExAC

AF:

0.0221

AC:

2684

Asia WGS

AF:

0.00347

AC:

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

.;T

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.63

T;T

MetaRNN

Benign

0.0050

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.3

.;M

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.29

.;N

REVEL

Benign

0.070

Sift

Benign

0.12

.;T

Sift4G

Benign

0.30

.;T

Polyphen

0.12

.;B

Vest4

0.12

MPC

0.19

ClinPred

0.015

GERP RS

3.4

Varity_R

0.045

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over