4-143999485-A-T

Variant names:

• chr4-143999485-A-T
• rs7662277
• NM_002100.6:c.137-36T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002100.6(GYPB):​c.137-36T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 1,146,142 control chromosomes in the GnomAD database, including 44,887 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 0.27 (6532 hom., cov: 32)
  • Exomes 𝑓: 0.27 (38355 hom.)
• Consequence: GYPB NM_002100.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.848
• Publications: 11 publications found

Genes affected

GYPB (HGNC:4703): (glycophorin B (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. GYPB gene consists of 5 exons and has 97% sequence homology with GYPA from the 5' UTR to the coding sequence encoding the first 45 amino acids. 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; also, 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. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

GUSBP5 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002100.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GYPB	NM_002100.6	MANE Select	c.137-36T>A		intron	N/A	NP_002091.4
	GYPB	NM_001304382.1		c.59-36T>A		intron	N/A	NP_001291311.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GYPB	ENST00000502664.6	TSL:1 MANE Select	c.137-36T>A		intron	N/A	ENSP00000427690.1
	GYPB	ENST00000506516.6	TSL:1	c.59-36T>A		intron	N/A	ENSP00000424025.2
	GYPB	ENST00000429670.3	TSL:1	c.137-36T>A		intron	N/A	ENSP00000394200.2

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41406 AN: 151174 Hom.: 6525 Cov.: 32

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.0417

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.292

GnomAD2 exomes AF: 0.310 AC: 68749 AN: 221634 AF XY: 0.316

Gnomad AFR exome AF: 0.201

Gnomad AMR exome AF: 0.362

Gnomad ASJ exome AF: 0.361

Gnomad EAS exome AF: 0.0376

Gnomad FIN exome AF: 0.334

Gnomad NFE exome AF: 0.331

Gnomad OTH exome AF: 0.322

GnomAD4 exome AF: 0.271 AC: 270091 AN: 994852 Hom.: 38355 Cov.: 14 AF XY: 0.278 AC XY: 142603 AN XY: 512914

African (AFR) AF: 0.175 AC: 4061 AN: 23162

American (AMR) AF: 0.347 AC: 13961 AN: 40250

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 7802 AN: 22656

East Asian (EAS) AF: 0.0462 AC: 1733 AN: 37530

South Asian (SAS) AF: 0.341 AC: 25004 AN: 73220

European-Finnish (FIN) AF: 0.326 AC: 17033 AN: 52304

Middle Eastern (MID) AF: 0.361 AC: 1726 AN: 4784

European-Non Finnish (NFE) AF: 0.268 AC: 186370 AN: 696194

Other (OTH) AF: 0.277 AC: 12401 AN: 44752

GnomAD4 genome AF: 0.274 AC: 41431 AN: 151290 Hom.: 6532 Cov.: 32 AF XY: 0.276 AC XY: 20408 AN XY: 73966

African (AFR) AF: 0.191 AC: 7779 AN: 40700

American (AMR) AF: 0.323 AC: 4929 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1212 AN: 3472

East Asian (EAS) AF: 0.0418 AC: 216 AN: 5172

South Asian (SAS) AF: 0.334 AC: 1607 AN: 4816

European-Finnish (FIN) AF: 0.328 AC: 3473 AN: 10586

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.314 AC: 21364 AN: 67980

Other (OTH) AF: 0.289 AC: 609 AN: 2110

Alfa AF: 0.305 Hom.: 1372

Bravo AF: 0.268

Asia WGS AF: 0.206 AC: 721 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.28
DANN	Benign	0.35
PhyloP100		-0.85
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Mutation Taster		=100/0	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: rs7662277; hg19: chr4-144920638; COSMIC: COSV51635110; COSMIC: COSV51635110;