rs8193

Variant names:

• chr11-35229771-C-T
• rs8193
• NM_000610.4:c.*438C>T

Variant summary

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

The NM_000610.4(CD44):​c.*438C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 175,070 control chromosomes in the GnomAD database, including 9,503 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 0.30 (7971 hom., cov: 32)
  • Exomes 𝑓: 0.35 (1532 hom.)
• Consequence: CD44 NM_000610.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.145
• Publications: 42 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 (SAS) allele frequency at 95% confidence interval = 0.586 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.*438C>T		3_prime_UTR	Exon 18 of 18	NP_000601.3
	CD44	NM_001440324.1		c.*438C>T		3_prime_UTR	Exon 18 of 18	NP_001427253.1
	CD44	NM_001440325.1		c.*438C>T		3_prime_UTR	Exon 18 of 18	NP_001427254.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD44	ENST00000428726.8	TSL:1 MANE Select	c.*438C>T		3_prime_UTR	Exon 18 of 18	ENSP00000398632.2	P16070-1
	CD44	ENST00000433892.6	TSL:1	c.*438C>T		3_prime_UTR	Exon 12 of 12	ENSP00000392331.2	P16070-10
	CD44	ENST00000263398.11	TSL:1	c.*438C>T		3_prime_UTR	Exon 9 of 9	ENSP00000263398.6	P16070-12

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44895 AN: 151968 Hom.: 7974 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.605

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.323

GnomAD4 exome AF: 0.348 AC: 7992 AN: 22984 Hom.: 1532 Cov.: 0 AF XY: 0.354 AC XY: 4277 AN XY: 12080

African (AFR) AF: 0.105 AC: 62 AN: 588

American (AMR) AF: 0.345 AC: 973 AN: 2824

Ashkenazi Jewish (ASJ) AF: 0.435 AC: 219 AN: 504

East Asian (EAS) AF: 0.368 AC: 551 AN: 1496

South Asian (SAS) AF: 0.518 AC: 1040 AN: 2006

European-Finnish (FIN) AF: 0.309 AC: 337 AN: 1090

Middle Eastern (MID) AF: 0.333 AC: 22 AN: 66

European-Non Finnish (NFE) AF: 0.333 AC: 4421 AN: 13292

Other (OTH) AF: 0.328 AC: 367 AN: 1118

GnomAD4 genome AF: 0.295 AC: 44892 AN: 152086 Hom.: 7971 Cov.: 32 AF XY: 0.303 AC XY: 22498 AN XY: 74334

African (AFR) AF: 0.111 AC: 4598 AN: 41504

American (AMR) AF: 0.325 AC: 4961 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 1634 AN: 3470

East Asian (EAS) AF: 0.414 AC: 2139 AN: 5166

South Asian (SAS) AF: 0.604 AC: 2917 AN: 4826

European-Finnish (FIN) AF: 0.337 AC: 3556 AN: 10558

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.352 AC: 23920 AN: 67978

Other (OTH) AF: 0.322 AC: 680 AN: 2114

Alfa AF: 0.334 Hom.: 21719

Bravo AF: 0.283

Asia WGS AF: 0.450 AC: 1562 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.66
DANN	Benign	0.23
PhyloP100		-0.14
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: rs8193; hg19: chr11-35251318;