11-35163276-G-C

Variant names:

• chr11-35163276-G-C
• rs353635
• NM_000610.4:c.68-13299G>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.68-13299G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 151,132 control chromosomes in the GnomAD database, including 23,983 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 (23983 hom., cov: 28)
• Consequence: CD44 NM_000610.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.298
• Publications: 8 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.75 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD44	NM_000610.4	MANE Select	c.68-13299G>C		intron	N/A	NP_000601.3
	CD44	NM_001440324.1		c.68-13299G>C		intron	N/A	NP_001427253.1
	CD44	NM_001440325.1		c.68-13299G>C		intron	N/A	NP_001427254.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD44	ENST00000428726.8	TSL:1 MANE Select	c.68-13299G>C		intron	N/A	ENSP00000398632.2
	CD44	ENST00000415148.6	TSL:1	c.68-13299G>C		intron	N/A	ENSP00000389830.2
	CD44	ENST00000433892.6	TSL:1	c.68-13299G>C		intron	N/A	ENSP00000392331.2

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82245 AN: 151018 Hom.: 23929 Cov.: 28

Gnomad AFR AF: 0.757

Gnomad AMI AF: 0.450

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.532

Gnomad FIN AF: 0.397

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.542

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

GnomAD4 genome AF: 0.545 AC: 82369 AN: 151132 Hom.: 23983 Cov.: 28 AF XY: 0.543 AC XY: 40096 AN XY: 73806

African (AFR) AF: 0.757 AC: 31117 AN: 41096

American (AMR) AF: 0.557 AC: 8469 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 1648 AN: 3464

East Asian (EAS) AF: 0.292 AC: 1503 AN: 5144

South Asian (SAS) AF: 0.532 AC: 2554 AN: 4798

European-Finnish (FIN) AF: 0.397 AC: 4110 AN: 10346

Middle Eastern (MID) AF: 0.538 AC: 157 AN: 292

European-Non Finnish (NFE) AF: 0.461 AC: 31260 AN: 67790

Other (OTH) AF: 0.545 AC: 1143 AN: 2096

Alfa AF: 0.501 Hom.: 2446

Bravo AF: 0.563

Asia WGS AF: 0.449 AC: 1563 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.31
PhyloP100		-0.30
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: rs353635; hg19: chr11-35184823; COSMIC: COSV53536385;