rs707974

Positions:

• chr6-31661722-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.*544T>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 0.0674 in 167,066 control chromosomes in the GnomAD database, including 534 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 0.067 (477 hom., cov: 32)
  • Exomes 𝑓: 0.071 (57 hom.)
• Consequence: GPANK1 NM_033177.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.132

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0962 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPANK1	NM_033177.4	c.*544T>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.*544T>C		3_prime_UTR_variant	3/3	1	NM_033177.4	ENSP00000365060	P1
GPANK1	ENST00000375906.5	c.*544T>C		3_prime_UTR_variant	4/4	2		ENSP00000365071	P1

Frequencies

GnomAD3 genomes AF: 0.0672 AC: 10217 AN: 152082 Hom.: 476 Cov.: 32

Gnomad AFR AF: 0.0190

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.0631

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.0183

Gnomad SAS AF: 0.0367

Gnomad FIN AF: 0.0670

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0981

Gnomad OTH AF: 0.0738

GnomAD4 exome AF: 0.0707 AC: 1052 AN: 14870 Hom.: 57 Cov.: 0 AF XY: 0.0688 AC XY: 710 AN XY: 10324

Gnomad4 AFR exome AF: 0.0240

Gnomad4 AMR exome AF: 0.0186

Gnomad4 ASJ exome AF: 0.152

Gnomad4 EAS exome AF: 0.0537

Gnomad4 SAS exome AF: 0.0335

Gnomad4 FIN exome AF: 0.0579

Gnomad4 NFE exome AF: 0.0882

Gnomad4 OTH exome AF: 0.0495

GnomAD4 genome AF: 0.0671 AC: 10213 AN: 152196 Hom.: 477 Cov.: 32 AF XY: 0.0655 AC XY: 4876 AN XY: 74414

Gnomad4 AFR AF: 0.0190

Gnomad4 AMR AF: 0.0630

Gnomad4 ASJ AF: 0.143

Gnomad4 EAS AF: 0.0183

Gnomad4 SAS AF: 0.0367

Gnomad4 FIN AF: 0.0670

Gnomad4 NFE AF: 0.0981

Gnomad4 OTH AF: 0.0735

Alfa AF: 0.0911 Hom.: 544

Bravo AF: 0.0651

Asia WGS AF: 0.0290 AC: 103 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.4
DANN	Benign	0.60

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: rs707974; hg19: chr6-31629499;