6-31662176-A-G

Position:

• chr6-31662176-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033177.4(GPANK1):​c.*90T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 806,402 control chromosomes in the GnomAD database, including 41,672 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 0.38 (11812 hom., cov: 32)
  • Exomes 𝑓: 0.29 (29860 hom.)
• Consequence: GPANK1 NM_033177.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.108

Genes affected

GPANK1 (HGNC:13920): (G-patch domain and ankyrin repeats 1) This gene is located in a cluster of HLA-B-associated transcripts, which is included in the human major histocompatability complex III region. This gene encodes a protein which is thought to play a role in immunity. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Nov 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPANK1	NM_033177.4	c.*90T>C		3_prime_UTR_variant	3/3	ENST00000375896.9	NP_149417.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPANK1	ENST00000375896.9	c.*90T>C		3_prime_UTR_variant	3/3	1	NM_033177.4	ENSP00000365060	P1

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57076 AN: 151942 Hom.: 11797 Cov.: 32

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.261

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.382

GnomAD4 exome AF: 0.291 AC: 190359 AN: 654342 Hom.: 29860 Cov.: 9 AF XY: 0.286 AC XY: 96846 AN XY: 338140

Gnomad4 AFR exome AF: 0.553

Gnomad4 AMR exome AF: 0.400

Gnomad4 ASJ exome AF: 0.299

Gnomad4 EAS exome AF: 0.412

Gnomad4 SAS exome AF: 0.282

Gnomad4 FIN exome AF: 0.397

Gnomad4 NFE exome AF: 0.254

Gnomad4 OTH exome AF: 0.304

GnomAD4 genome AF: 0.376 AC: 57134 AN: 152060 Hom.: 11812 Cov.: 32 AF XY: 0.382 AC XY: 28384 AN XY: 74336

Gnomad4 AFR AF: 0.553

Gnomad4 AMR AF: 0.393

Gnomad4 ASJ AF: 0.297

Gnomad4 EAS AF: 0.383

Gnomad4 SAS AF: 0.311

Gnomad4 FIN AF: 0.420

Gnomad4 NFE AF: 0.266

Gnomad4 OTH AF: 0.381

Alfa AF: 0.284 Hom.: 9460

Bravo AF: 0.385

Asia WGS AF: 0.358 AC: 1241 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.1
DANN	Benign	0.62

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: rs7029; hg19: chr6-31629953; COSMIC: COSV63263614; COSMIC: COSV63263614;