4-144009062-G-T

Variant names:

• chr4-144009062-G-T
• rs9685167
• NM_002100.6:c.38-7779C>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.38-7779C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.861 in 151,250 control chromosomes in the GnomAD database, including 59,439 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 0.86 (59439 hom., cov: 32)
• Consequence: GYPB NM_002100.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.799
• Publications: 1 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.988 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GYPB	NM_002100.6	c.38-7779C>A		intron_variant	Intron 1 of 4	ENST00000502664.6	NP_002091.4
GYPB	NM_001304382.1	c.-42+7740C>A		intron_variant	Intron 2 of 5		NP_001291311.1
GYPB	XM_011531903.3	c.38-7779C>A		intron_variant	Intron 1 of 4		XP_011530205.1
GYPB	XM_011531904.4	c.-114-6368C>A		intron_variant	Intron 1 of 5		XP_011530206.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GYPB	ENST00000502664.6	c.38-7779C>A		intron_variant	Intron 1 of 4	1	NM_002100.6	ENSP00000427690.1
GYPB	ENST00000504951.6	n.38-6368C>A		intron_variant	Intron 1 of 6	1		ENSP00000421974.2

Frequencies

GnomAD3 genomes AF: 0.861 AC: 130137 AN: 151134 Hom.: 59430 Cov.: 32

Gnomad AFR AF: 0.555

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.915

Gnomad ASJ AF: 0.958

Gnomad EAS AF: 0.853

Gnomad SAS AF: 0.984

Gnomad FIN AF: 0.991

Gnomad MID AF: 0.946

Gnomad NFE AF: 0.995

Gnomad OTH AF: 0.883

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.861 AC: 130177 AN: 151250 Hom.: 59439 Cov.: 32 AF XY: 0.864 AC XY: 63904 AN XY: 73998

African (AFR) AF: 0.554 AC: 22481 AN: 40550

American (AMR) AF: 0.915 AC: 13986 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.958 AC: 3325 AN: 3472

East Asian (EAS) AF: 0.853 AC: 4418 AN: 5178

South Asian (SAS) AF: 0.985 AC: 4749 AN: 4822

European-Finnish (FIN) AF: 0.991 AC: 10521 AN: 10620

Middle Eastern (MID) AF: 0.942 AC: 277 AN: 294

European-Non Finnish (NFE) AF: 0.995 AC: 67647 AN: 68018

Other (OTH) AF: 0.884 AC: 1861 AN: 2106

Alfa AF: 0.881 Hom.: 8547

Bravo AF: 0.838

Asia WGS AF: 0.889 AC: 3089 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.7
DANN	Benign	0.57
PhyloP100		0.80
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: rs9685167; hg19: chr4-144930215;