chr4-143997550-C-T

Variant names:

• chr4-143997550-C-T
• rs112711627
• NM_002100.6:c.260G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_002100.6(GYPB):​c.260G>A​(p.Arg87Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000527 in 1,571,680 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0023 (15 hom., cov: 32)
  • Exomes 𝑓: 0.00034 (14 hom.)
• Consequence: GYPB NM_002100.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.63
• Publications: 3 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0048134327).
• BP6: Variant 4-143997550-C-T is Benign according to our data. Variant chr4-143997550-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3388670.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 15 BG gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GYPB	NM_002100.6	MANE Select	c.260G>A	p.Arg87Gln	missense	Exon 4 of 5	NP_002091.4	P06028-1
	GYPB	NM_001304382.1		c.182G>A	p.Arg61Gln	missense	Exon 5 of 6	NP_001291311.1	P06028

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GYPB	ENST00000502664.6	TSL:1 MANE Select	c.260G>A	p.Arg87Gln	missense	Exon 4 of 5	ENSP00000427690.1	P06028-1
	GYPB	ENST00000506516.6	TSL:1	c.182G>A	p.Arg61Gln	missense	Exon 5 of 6	ENSP00000424025.2	D6RBP2
	GYPB	ENST00000429670.3	TSL:1	c.184G>A	p.Asp62Asn	missense	Exon 4 of 5	ENSP00000394200.2	E7ERJ5

Frequencies

GnomAD3 genomes AF: 0.00224 AC: 339 AN: 151112 Hom.: 15 Cov.: 32

Gnomad AFR AF: 0.00793

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000590

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000965

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000703 AC: 176 AN: 250306 AF XY: 0.000598

Gnomad AFR exome AF: 0.00929

Gnomad AMR exome AF: 0.000319

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000654

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000353

Gnomad OTH exome AF: 0.000494

GnomAD4 exome AF: 0.000343 AC: 487 AN: 1420452 Hom.: 14 Cov.: 25 AF XY: 0.000319 AC XY: 226 AN XY: 709494

African (AFR) AF: 0.00722 AC: 227 AN: 31454

American (AMR) AF: 0.000269 AC: 12 AN: 44624

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25846

East Asian (EAS) AF: 0.00373 AC: 147 AN: 39368

South Asian (SAS) AF: 0.0000235 AC: 2 AN: 85288

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53268

Middle Eastern (MID) AF: 0.000354 AC: 2 AN: 5656

European-Non Finnish (NFE) AF: 0.0000548 AC: 59 AN: 1076162

Other (OTH) AF: 0.000646 AC: 38 AN: 58786

GnomAD4 genome AF: 0.00226 AC: 342 AN: 151228 Hom.: 15 Cov.: 32 AF XY: 0.00222 AC XY: 164 AN XY: 73942

African (AFR) AF: 0.00798 AC: 324 AN: 40590

American (AMR) AF: 0.000589 AC: 9 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000967 AC: 5 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10582

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68020

Other (OTH) AF: 0.00143 AC: 3 AN: 2102

Alfa AF: 0.00115 Hom.: 5

ESP6500AA AF: 0.0114 AC: 50

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000923 AC: 112

Asia WGS AF: 0.00231 AC: 8 AN: 3476

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.66
DANN	Benign	0.90
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0039	N
LIST_S2	Benign	0.32	T
MetaRNN	Benign	0.0048	T
MetaSVM	Benign	-1.1	T
PhyloP100		-1.6
PROVEAN	Benign	-0.14	N
REVEL	Benign	0.012
Sift	Benign	0.043	D
Sift4G	Uncertain	0.031	D
Vest4		0.20
MVP		0.040
ClinPred		0.028	T
GERP RS		-4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.086
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs112711627; hg19: chr4-144918703; COSMIC: COSV99302694; COSMIC: COSV99302694;