4-144016195-C-T

Variant names:

• chr4-144016195-C-T
• rs4835511
• NM_002100.6:c.37+3056G>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.37+3056G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0758 in 131,096 control chromosomes in the GnomAD database, including 1,168 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 0.076 (1168 hom., cov: 27)
• Consequence: GYPB NM_002100.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.312
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.218 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GYPB	NM_002100.6	MANE Select	c.37+3056G>A		intron	N/A	NP_002091.4	P06028-1
	GYPB	NM_001304382.1		c.-42+607G>A		intron	N/A	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.37+3056G>A		intron	N/A	ENSP00000427690.1	P06028-1
	GYPB	ENST00000506516.6	TSL:1	c.-100+3056G>A		intron	N/A	ENSP00000424025.2	D6RBP2
	GYPB	ENST00000429670.3	TSL:1	c.37+3056G>A		intron	N/A	ENSP00000394200.2	E7ERJ5

Frequencies

GnomAD3 genomes AF: 0.0757 AC: 9915 AN: 131026 Hom.: 1166 Cov.: 27

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0653

Gnomad ASJ AF: 0.0445

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.0172

Gnomad FIN AF: 0.0112

Gnomad MID AF: 0.0367

Gnomad NFE AF: 0.00428

Gnomad OTH AF: 0.0737

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

GnomAD4 genome AF: 0.0758 AC: 9933 AN: 131096 Hom.: 1168 Cov.: 27 AF XY: 0.0775 AC XY: 4834 AN XY: 62386

African (AFR) AF: 0.223 AC: 7699 AN: 34580

American (AMR) AF: 0.0653 AC: 809 AN: 12380

Ashkenazi Jewish (ASJ) AF: 0.0445 AC: 147 AN: 3304

East Asian (EAS) AF: 0.170 AC: 725 AN: 4274

South Asian (SAS) AF: 0.0169 AC: 64 AN: 3786

European-Finnish (FIN) AF: 0.0112 AC: 74 AN: 6602

Middle Eastern (MID) AF: 0.0385 AC: 8 AN: 208

European-Non Finnish (NFE) AF: 0.00428 AC: 271 AN: 63260

Other (OTH) AF: 0.0738 AC: 136 AN: 1842

Alfa AF: 0.0515 Hom.: 106

Asia WGS AF: 0.0880 AC: 307 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.53
DANN	Benign	0.52
PhyloP100		-0.31
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: rs4835511; hg19: chr4-144937348;