6-31575254-G-A

Variant names:

• chr6-31575254-G-A
• rs1800629

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The variant allele was found at a frequency of 0.131 in 474,386 control chromosomes in the GnomAD database, including 4,807 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as drug response (★★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1582 hom., cov: 31)
  • Exomes 𝑓: 0.13 (3225 hom.)
• Consequence: Unknown
• Clinical Significance: drug response reviewed by expert panel U:2 O:9
• Conservation: PhyloP100: 0.0180
• Publications: 3792 publications found

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Variant Effect in Transcripts

 

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20989 AN: 152008 Hom.: 1578 Cov.: 31

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.0872

Gnomad ASJ AF: 0.0839

Gnomad EAS AF: 0.0681

Gnomad SAS AF: 0.0691

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.126

GnomAD2 exomes AF: 0.116 AC: 17554 AN: 150892 AF XY: 0.118

Gnomad AFR exome AF: 0.119

Gnomad AMR exome AF: 0.0594

Gnomad ASJ exome AF: 0.0762

Gnomad EAS exome AF: 0.0896

Gnomad FIN exome AF: 0.120

Gnomad NFE exome AF: 0.163

Gnomad OTH exome AF: 0.124

GnomAD4 exome AF: 0.128 AC: 41363 AN: 322260 Hom.: 3225 Cov.: 0 AF XY: 0.125 AC XY: 22845 AN XY: 183234

African (AFR) AF: 0.123 AC: 1151 AN: 9350

American (AMR) AF: 0.0609 AC: 1749 AN: 28742

Ashkenazi Jewish (ASJ) AF: 0.0803 AC: 903 AN: 11246

East Asian (EAS) AF: 0.0760 AC: 806 AN: 10602

South Asian (SAS) AF: 0.0760 AC: 4580 AN: 60236

European-Finnish (FIN) AF: 0.134 AC: 1878 AN: 14012

Middle Eastern (MID) AF: 0.170 AC: 481 AN: 2824

European-Non Finnish (NFE) AF: 0.163 AC: 27754 AN: 169932

Other (OTH) AF: 0.135 AC: 2061 AN: 15316

GnomAD4 genome AF: 0.138 AC: 20992 AN: 152126 Hom.: 1582 Cov.: 31 AF XY: 0.132 AC XY: 9824 AN XY: 74368

African (AFR) AF: 0.127 AC: 5287 AN: 41508

American (AMR) AF: 0.0870 AC: 1330 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0839 AC: 291 AN: 3470

East Asian (EAS) AF: 0.0683 AC: 353 AN: 5168

South Asian (SAS) AF: 0.0690 AC: 332 AN: 4814

European-Finnish (FIN) AF: 0.123 AC: 1299 AN: 10604

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11606 AN: 67968

Other (OTH) AF: 0.124 AC: 262 AN: 2108

Alfa AF: 0.156 Hom.: 6420

Bravo AF: 0.135

Asia WGS AF: 0.0700 AC: 243 AN: 3478

ClinVar

ClinVar submissions

Significance: drug response

Revision: reviewed by expert panel

Pathogenic	VUS	Benign	Condition
-	1	-	Susceptibility to severe coronavirus disease (COVID-19) (1)
-	1	-	Susceptibility to severe coronavirus disease (COVID-19) due to high plasma levels of TNF, TNFR, and/or TNFR4 (1)
-	-	-	Endometriosis (1)
-	-	-	etanercept response - Efficacy (1)
-	-	-	HUMAN IMMUNODEFICIENCY VIRUS DEMENTIA, SUSCEPTIBILITY TO (1)
-	-	-	Inherited susceptibility to asthma (1)
-	-	-	Malaria, cerebral, susceptibility to (1)
-	-	-	MIGRAINE WITHOUT AURA, SUSCEPTIBILITY TO (1)
-	-	-	Psoriatic arthritis, susceptibility to (1)
-	-	-	SEPTIC SHOCK, SUSCEPTIBILITY TO (1)
-	-	-	Systemic lupus erythematosus, susceptibility to (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.9
DANN	Benign	0.48
PhyloP100		0.018
PromoterAI		-0.028	Neutral

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1800629; hg19: chr6-31543031;