chr4-144120567-A-G

Position:

• chr4-144120567-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

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. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• 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

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0034795105).
• BP6: Variant 4-144120567-A-G is Benign according to our data. Variant chr4-144120567-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GYPA	NM_002099.8	c.59T>C	p.Leu20Ser	missense_variant	2/7	ENST00000641688.3	NP_002090.4
LOC105377460	XR_002959803.2	n.5270+5338A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GYPA	ENST00000641688.3	c.59T>C	p.Leu20Ser	missense_variant	2/7		NM_002099.8	ENSP00000493142	P4

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

GnomAD3 exomes AF: 0.254 AC: 34637 AN: 136582 Hom.: 15137 AF XY: 0.248 AC XY: 17927 AN XY: 72390

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 SAS exome AF: 0.328

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

Gnomad4 AFR exome AF: 0.241

Gnomad4 AMR exome AF: 0.478

Gnomad4 ASJ exome AF: 0.405

Gnomad4 EAS exome AF: 0.426

Gnomad4 SAS exome AF: 0.544

Gnomad4 FIN exome AF: 0.462

Gnomad4 NFE exome AF: 0.277

Gnomad4 OTH exome AF: 0.356

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

Gnomad4 AFR AF: 0.381

Gnomad4 AMR AF: 0.485

Gnomad4 ASJ AF: 0.492

Gnomad4 EAS AF: 0.445

Gnomad4 SAS AF: 0.477

Gnomad4 FIN AF: 0.540

Gnomad4 NFE AF: 0.481

Gnomad4 OTH AF: 0.402

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 v4.3

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;T;.;.;T;.;.
Eigen	Benign	-1.8
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0015	N
LIST_S2	Benign	0.47	T;.;T;T;.;T;T;T
MetaRNN	Benign	0.0035	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.92	T
MutationTaster	Benign	1.0	P;P;P;P;P;P;P;P
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.69	.;.;N;.;.;N;N;N
REVEL	Benign	0.0030
Sift	Benign	0.16	.;.;T;.;.;T;T;T
Sift4G	Benign	0.38	T;.;T;.;T;T;T;T
Polyphen		0.0	.;.;.;.;.;B;B;.
Vest4		0.043
MPC		0.021
ClinPred		0.0040	T
GERP RS		-3.4
gMVP		0.013

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