rs7682260

Variant names:

• chr4-144120567-A-G
• rs7682260
• NM_002099.8:c.59T>C

Your query was ambiguous. Multiple possible variants found:

• chr4-144120567-A-G
• chr4-144120567-A-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_002099.8(GYPA):​c.59T>C​(p.Leu20Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 865,936 control chromosomes in the GnomAD database, including 99,220 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.46 (12545 hom., cov: 19)
  • Exomes 𝑓: 0.32 (86675 hom.)
• Consequence: GYPA NM_002099.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.112
• Publications: 25 publications found

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]

ENSG00000285783 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0034795105).
• BS2: High Homozygotes in GnomAd4 at 12545 BG gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002099.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GYPA	NM_002099.8	MANE Select	c.59T>C	p.Leu20Ser	missense	Exon 2 of 7	NP_002090.4
	GYPA	NM_001438046.1		c.59T>C	p.Leu20Ser	missense	Exon 2 of 6	NP_001424975.1
	GYPA	NM_001308187.2		c.59T>C	p.Leu20Ser	missense	Exon 2 of 6	NP_001295116.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GYPA	ENST00000641688.3	MANE Select	c.59T>C	p.Leu20Ser	missense	Exon 2 of 7	ENSP00000493142.2
	GYPA	ENST00000360771.8	TSL:1	c.59T>C	p.Leu20Ser	missense	Exon 2 of 7	ENSP00000354003.4
	GYPA	ENST00000535709.6	TSL:1	c.53T>C	p.Leu18Ser	missense	Exon 3 of 8	ENSP00000445398.2

Frequencies

GnomAD3 genomes AF: 0.455 AC: 49394 AN: 108490 Hom.: 12529 Cov.: 19

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.410

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.492

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.540

Gnomad MID AF: 0.564

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.406

GnomAD2 exomes AF: 0.254 AC: 34637 AN: 136582 AF XY: 0.248

Gnomad AFR exome AF: 0.179

Gnomad AMR exome AF: 0.394

Gnomad ASJ exome AF: 0.260

Gnomad EAS exome AF: 0.324

Gnomad FIN exome AF: 0.210

Gnomad NFE exome AF: 0.198

Gnomad OTH exome AF: 0.329

GnomAD4 exome AF: 0.321 AC: 243196 AN: 757344 Hom.: 86675 Cov.: 30 AF XY: 0.331 AC XY: 126817 AN XY: 383684

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.241 AC: 5261 AN: 21804

American (AMR) AF: 0.478 AC: 12674 AN: 26530

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 6059 AN: 14972

East Asian (EAS) AF: 0.426 AC: 10306 AN: 24194

South Asian (SAS) AF: 0.544 AC: 29501 AN: 54186

European-Finnish (FIN) AF: 0.462 AC: 14882 AN: 32202

Middle Eastern (MID) AF: 0.311 AC: 961 AN: 3094

European-Non Finnish (NFE) AF: 0.277 AC: 152027 AN: 547964

Other (OTH) AF: 0.356 AC: 11525 AN: 32398

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.455 AC: 49435 AN: 108592 Hom.: 12545 Cov.: 19 AF XY: 0.456 AC XY: 23648 AN XY: 51906

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.381 AC: 11328 AN: 29736

American (AMR) AF: 0.485 AC: 5040 AN: 10398

Ashkenazi Jewish (ASJ) AF: 0.492 AC: 1282 AN: 2606

East Asian (EAS) AF: 0.445 AC: 1585 AN: 3562

South Asian (SAS) AF: 0.477 AC: 1354 AN: 2838

European-Finnish (FIN) AF: 0.540 AC: 3665 AN: 6792

Middle Eastern (MID) AF: 0.578 AC: 133 AN: 230

European-Non Finnish (NFE) AF: 0.481 AC: 24171 AN: 50262

Other (OTH) AF: 0.402 AC: 594 AN: 1478

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.418 Hom.: 2331

ESP6500AA AF: 0.173 AC: 737

ESP6500EA AF: 0.240 AC: 1997

ExAC AF: 0.162 AC: 15521

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.037
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	11
DANN	Benign	0.42
DEOGEN2	Benign	0.0025	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0015	N
LIST_S2	Benign	0.47	T
MetaRNN	Benign	0.0035	T
MetaSVM	Benign	-0.92	T
PhyloP100		0.11
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.69	N
REVEL	Benign	0.0030
Sift	Benign	0.16	T
Sift4G	Benign	0.38	T
Polyphen		0.0	B
Vest4		0.043
MPC		0.021
ClinPred		0.0040	T
GERP RS		-3.4
gMVP		0.013
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7682260; hg19: chr4-145041720; COSMIC: COSV51619623; COSMIC: COSV51619623;