11-35162291-T-C

Variant names:

• chr11-35162291-T-C
• rs193276
• NM_000610.4:c.68-14284T>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.68-14284T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 152,112 control chromosomes in the GnomAD database, including 5,050 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 0.26 (5050 hom., cov: 32)
• Consequence: CD44 NM_000610.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.842
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.285 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.68-14284T>C		intron	N/A	NP_000601.3
	CD44	NM_001440324.1		c.68-14284T>C		intron	N/A	NP_001427253.1
	CD44	NM_001440325.1		c.68-14284T>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.68-14284T>C		intron	N/A	ENSP00000398632.2
	CD44	ENST00000415148.6	TSL:1	c.68-14284T>C		intron	N/A	ENSP00000389830.2
	CD44	ENST00000433892.6	TSL:1	c.68-14284T>C		intron	N/A	ENSP00000392331.2

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38939 AN: 151994 Hom.: 5034 Cov.: 32

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.256 AC: 38986 AN: 152112 Hom.: 5050 Cov.: 32 AF XY: 0.258 AC XY: 19181 AN XY: 74368

African (AFR) AF: 0.289 AC: 11994 AN: 41482

American (AMR) AF: 0.268 AC: 4095 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 558 AN: 3472

East Asian (EAS) AF: 0.120 AC: 624 AN: 5182

South Asian (SAS) AF: 0.234 AC: 1129 AN: 4820

European-Finnish (FIN) AF: 0.301 AC: 3182 AN: 10564

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.244 AC: 16570 AN: 67988

Other (OTH) AF: 0.254 AC: 536 AN: 2112

Alfa AF: 0.243 Hom.: 16626

Bravo AF: 0.257

Asia WGS AF: 0.208 AC: 728 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.11
DANN	Benign	0.56
PhyloP100		-0.84
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: rs193276; hg19: chr11-35183838;