rs4755392

Variant names:

• chr11-35232539-T-A
• rs4755392
• NM_000610.4:c.*3206T>A

Your query was ambiguous. Multiple possible variants found:

• chr11-35232539-T-A
• chr11-35232539-T-C

Variant summary

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

The NM_000610.4(CD44):​c.*3206T>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 151,872 control chromosomes in the GnomAD database, including 13,999 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 0.42 (13999 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: CD44 NM_000610.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.467
• Publications: 4 publications found

Genes affected

CD44 (HGNC:1681): (CD44 molecule (IN blood group)) The protein encoded by this gene is a cell-surface glycoprotein involved in cell-cell interactions, cell adhesion and migration. It is a receptor for hyaluronic acid (HA) and can also interact with other ligands, such as osteopontin, collagens, and matrix metalloproteinases (MMPs). This protein participates in a wide variety of cellular functions including lymphocyte activation, recirculation and homing, hematopoiesis, and tumor metastasis. Transcripts for this gene undergo complex alternative splicing that results in many functionally distinct isoforms, however, the full length nature of some of these variants has not been determined. Alternative splicing is the basis for the structural and functional diversity of this protein, and may be related to tumor metastasis. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD44	NM_000610.4	c.*3206T>A		downstream_gene_variant		ENST00000428726.8	NP_000601.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD44	ENST00000428726.8	c.*3206T>A		downstream_gene_variant		1	NM_000610.4	ENSP00000398632.2
CD44	ENST00000263398.11	c.*3206T>A		downstream_gene_variant		1		ENSP00000263398.6

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64352 AN: 151754 Hom.: 14005 Cov.: 31

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.555

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.561

Gnomad FIN AF: 0.489

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.428

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

GnomAD4 genome AF: 0.424 AC: 64363 AN: 151872 Hom.: 13999 Cov.: 31 AF XY: 0.430 AC XY: 31925 AN XY: 74218

African (AFR) AF: 0.322 AC: 13342 AN: 41438

American (AMR) AF: 0.394 AC: 6003 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.555 AC: 1924 AN: 3464

East Asian (EAS) AF: 0.458 AC: 2363 AN: 5154

South Asian (SAS) AF: 0.561 AC: 2696 AN: 4804

European-Finnish (FIN) AF: 0.489 AC: 5143 AN: 10528

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.461 AC: 31321 AN: 67920

Other (OTH) AF: 0.425 AC: 895 AN: 2108

Alfa AF: 0.300 Hom.: 795

Bravo AF: 0.407

Asia WGS AF: 0.463 AC: 1607 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.49
DANN	Benign	0.65
PhyloP100		-0.47

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4755392; hg19: chr11-35254086;