11-35160066-T-C

Variant names:

• chr11-35160066-T-C
• rs353644
• NM_000610.4:c.68-16509T>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.68-16509T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 152,080 control chromosomes in the GnomAD database, including 24,254 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 0.55 (24254 hom., cov: 32)
• Consequence: CD44 NM_000610.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.677
• Publications: 12 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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000610.4. 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
	CD44	NM_000610.4	MANE Select	c.68-16509T>C		intron	N/A	NP_000601.3
	CD44	NM_001440324.1		c.68-16509T>C		intron	N/A	NP_001427253.1
	CD44	NM_001440325.1		c.68-16509T>C		intron	N/A	NP_001427254.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD44	ENST00000428726.8	TSL:1 MANE Select	c.68-16509T>C		intron	N/A	ENSP00000398632.2	P16070-1
	CD44	ENST00000415148.6	TSL:1	c.68-16509T>C		intron	N/A	ENSP00000389830.2	P16070-4
	CD44	ENST00000433892.6	TSL:1	c.68-16509T>C		intron	N/A	ENSP00000392331.2	P16070-10

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82980 AN: 151960 Hom.: 24198 Cov.: 32

Gnomad AFR AF: 0.757

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.559

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.544

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

GnomAD4 genome AF: 0.546 AC: 83108 AN: 152080 Hom.: 24254 Cov.: 32 AF XY: 0.544 AC XY: 40465 AN XY: 74316

African (AFR) AF: 0.758 AC: 31423 AN: 41478

American (AMR) AF: 0.560 AC: 8558 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.477 AC: 1654 AN: 3466

East Asian (EAS) AF: 0.292 AC: 1510 AN: 5172

South Asian (SAS) AF: 0.534 AC: 2579 AN: 4826

European-Finnish (FIN) AF: 0.399 AC: 4219 AN: 10574

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.463 AC: 31436 AN: 67962

Other (OTH) AF: 0.546 AC: 1154 AN: 2112

Alfa AF: 0.487 Hom.: 39653

Bravo AF: 0.564

Asia WGS AF: 0.451 AC: 1569 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.7
DANN	Benign	0.82
PhyloP100		-0.68
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: rs353644; hg19: chr11-35181613;