rs7661933

Variant names:

• chr4-143999327-A-G
• rs7661933
• NM_002100.6:c.175+84T>C

Your query was ambiguous. Multiple possible variants found:

• chr4-143999327-A-G
• chr4-143999327-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002100.6(GYPB):​c.175+84T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000173 in 577,910 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: GYPB NM_002100.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.83
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).

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.175+84T>C		intron	N/A	NP_002091.4	P06028-1
	GYPB	NM_001304382.1		c.97+84T>C		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.175+84T>C		intron	N/A	ENSP00000427690.1	P06028-1
	GYPB	ENST00000506516.6	TSL:1	c.97+84T>C		intron	N/A	ENSP00000424025.2	D6RBP2
	GYPB	ENST00000429670.3	TSL:1	c.175+84T>C		intron	N/A	ENSP00000394200.2	E7ERJ5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000173 AC: 1 AN: 577910 Hom.: 0 Cov.: 7 AF XY: 0.00000320 AC XY: 1 AN XY: 312036

African (AFR) AF: 0.00 AC: 0 AN: 13818

American (AMR) AF: 0.00 AC: 0 AN: 27784

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19362

East Asian (EAS) AF: 0.00 AC: 0 AN: 32766

South Asian (SAS) AF: 0.00 AC: 0 AN: 58016

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49750

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3994

European-Non Finnish (NFE) AF: 0.00000293 AC: 1 AN: 341788

Other (OTH) AF: 0.00 AC: 0 AN: 30632

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.13
DANN	Benign	0.70
PhyloP100		-1.8

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: rs7661933; hg19: chr4-144920480;