rs34856868

chr1-92088726-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04

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]

ACMG classification

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. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 40 AR gene

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BTBD8	ENST00000636805.2	c.178G>A	p.Val60Ile	missense_variant	2/18	5	NM_001376131.1	P1
BTBD8	ENST00000342818.4	c.178G>A	p.Val60Ile	missense_variant	2/9	1
BTBD8	ENST00000370382.7	n.445G>A		non_coding_transcript_exon_variant	2/6	1
BTBD8	ENST00000635934.1	c.178G>A	p.Val60Ile	missense_variant, NMD_transcript_variant	2/17	5

Frequencies

GnomAD3 genomes AF: 0.0193 AC: 2936 AN: 152006 Hom.: 40 Cov.: 32

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.: 78 AF XY: 0.0200 AC XY: 2707 AN XY: 135446

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.: 31 AF XY: 0.0243 AC XY: 17618 AN XY: 725354

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.: 40 Cov.: 32 AF XY: 0.0193 AC XY: 1432 AN XY: 74344

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.: 83

Bravo AF: 0.0172

TwinsUK AF: 0.0310 AC: 115

ALSPAC AF: 0.0265 AC: 102

ESP6500AA AF: 0.00590 AC: 26

ESP6500EA AF: 0.0302 AC: 260

ExAC AF: 0.0221 AC: 2684

Asia WGS AF: 0.00347 AC: 12 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	T
BayesDel_noAF	Benign	-0.37
Cadd	Benign	15
Dann	Uncertain	0.99
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.63	T;T
MetaRNN	Benign	0.0050	T;T
MetaSVM	Benign	-0.90	T
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.32	T
Polyphen		0.12	.;B
Vest4		0.12
MPC		0.19
ClinPred		0.015	T
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

Other links and lift over

dbSNP: rs34856868; hg19: chr1-92554283;