rs7658293

chr4-144120554-C-Achr4-144120554-C-G

Variant summary

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

The NM_002099.8(GYPA):c.72G>T(p.Glu24Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 999,138 control chromosomes in the GnomAD database, including 74,231 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.45 (11689 hom., cov: 19)
  • Exomes 𝑓: 0.20 (62542 hom.)
• Consequence: GYPA NM_002099.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.682

Genes affected

GYPA (HGNC:4702): (glycophorin A (MNS blood group)) Glycophorins A (GYPA) and B (GYPB) are major sialoglycoproteins of the human erythrocyte membrane which bear the antigenic determinants for the MN and Ss blood groups. In addition to the M or N and S or s antigens that commonly occur in all populations, about 40 related variant phenotypes have been identified. These variants include all the variants of the Miltenberger complex and several isoforms of Sta, as well as Dantu, Sat, He, Mg, and deletion variants Ena, S-s-U- and Mk. Most of the variants are the result of gene recombinations between GYPA and GYPB. [provided by RefSeq, Jul 2008]

LOC105377460 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=6.982088E-4).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GYPA	NM_002099.8	c.72G>T	p.Glu24Asp	missense_variant	2/7	ENST00000641688.3
LOC105377460	XR_002959803.2	n.5270+5325C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GYPA	ENST00000641688.3	c.72G>T	p.Glu24Asp	missense_variant	2/7		NM_002099.8	P4

Frequencies

GnomAD3 genomes AF: 0.451 AC: 47020 AN: 104240 Hom.: 11673 Cov.: 19

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.489

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.409

GnomAD3 exomes AF: 0.129 AC: 20346 AN: 157362 Hom.: 9019 AF XY: 0.119 AC XY: 10109 AN XY: 85064

Gnomad AFR exome AF: 0.134

Gnomad AMR exome AF: 0.240

Gnomad ASJ exome AF: 0.0861

Gnomad EAS exome AF: 0.241

Gnomad SAS exome AF: 0.144

Gnomad FIN exome AF: 0.0493

Gnomad NFE exome AF: 0.0934

Gnomad OTH exome AF: 0.188

GnomAD4 exome AF: 0.200 AC: 178520 AN: 894792 Hom.: 62542 Cov.: 29 AF XY: 0.211 AC XY: 94518 AN XY: 446930

Gnomad4 AFR exome AF: 0.174

Gnomad4 AMR exome AF: 0.339

Gnomad4 ASJ exome AF: 0.301

Gnomad4 EAS exome AF: 0.425

Gnomad4 SAS exome AF: 0.431

Gnomad4 FIN exome AF: 0.468

Gnomad4 NFE exome AF: 0.148

Gnomad4 OTH exome AF: 0.259

GnomAD4 genome AF: 0.451 AC: 47062 AN: 104346 Hom.: 11689 Cov.: 19 AF XY: 0.451 AC XY: 22417 AN XY: 49752

Gnomad4 AFR AF: 0.381

Gnomad4 AMR AF: 0.482

Gnomad4 ASJ AF: 0.489

Gnomad4 EAS AF: 0.441

Gnomad4 SAS AF: 0.474

Gnomad4 FIN AF: 0.533

Gnomad4 NFE AF: 0.475

Gnomad4 OTH AF: 0.404

Alfa AF: 0.534 Hom.: 2784

ExAC AF: 0.0194 AC: 1695

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
Cadd	Benign	0.77
Dann	Benign	0.42
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.00093	N
LIST_S2	Benign	0.54	T;.;T;T;.;T;T;T
MetaRNN	Benign	0.00070	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationTaster	Benign	1.0	P;P;P;P;P;P;P;P
PrimateAI	Benign	0.23	T
Sift4G	Benign	0.64	T;.;T;.;T;T;T;T
Polyphen		0.61, 0.010	.;.;.;.;.;P;B;.
Vest4		0.053
MutPred		0.31		.;Loss of glycosylation at T23 (P = 0.0157);Loss of glycosylation at T23 (P = 0.0157);Loss of glycosylation at T23 (P = 0.0157);.;Loss of glycosylation at T23 (P = 0.0157);Loss of glycosylation at T23 (P = 0.0157);Loss of glycosylation at T23 (P = 0.0157);
MPC		0.040
ClinPred		0.0073	T
GERP RS		-1.8
gMVP		0.018

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: rs7658293; hg19: chr4-145041707; COSMIC: COSV51629959; COSMIC: COSV51629959;