chr11-35222497-G-C

Variant names:

• chr11-35222497-G-C
• rs7116739
• ENST00000442151.6:c.*119G>C

Variant summary

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

The NM_001202557.2(CD44):​c.*119G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.702 in 1,197,992 control chromosomes in the GnomAD database, including 297,505 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 0.72 (39366 hom., cov: 29)
  • Exomes 𝑓: 0.70 (258139 hom.)
• Consequence: CD44 NM_001202557.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.976
• Publications: 15 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001202557.2. 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.2024+765G>C		intron	N/A	NP_000601.3
	CD44	NM_001202557.2		c.*119G>C		3_prime_UTR	Exon 9 of 9	NP_001189486.1
	CD44	NM_001440324.1		c.2027+765G>C		intron	N/A	NP_001427253.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD44	ENST00000442151.6	TSL:1	c.*119G>C		3_prime_UTR	Exon 9 of 9	ENSP00000398099.2
	CD44	ENST00000428726.8	TSL:1 MANE Select	c.2024+765G>C		intron	N/A	ENSP00000398632.2
	CD44	ENST00000415148.6	TSL:1	c.1895+765G>C		intron	N/A	ENSP00000389830.2

Frequencies

GnomAD3 genomes AF: 0.718 AC: 108658 AN: 151266 Hom.: 39329 Cov.: 29

Gnomad AFR AF: 0.684

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.773

Gnomad ASJ AF: 0.745

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.836

Gnomad FIN AF: 0.786

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.686

Gnomad OTH AF: 0.702

GnomAD4 exome AF: 0.700 AC: 732228 AN: 1046630 Hom.: 258139 Cov.: 19 AF XY: 0.703 AC XY: 357397 AN XY: 508174

African (AFR) AF: 0.695 AC: 14272 AN: 20546

American (AMR) AF: 0.845 AC: 13130 AN: 15530

Ashkenazi Jewish (ASJ) AF: 0.738 AC: 9142 AN: 12394

East Asian (EAS) AF: 0.997 AC: 10503 AN: 10536

South Asian (SAS) AF: 0.823 AC: 49250 AN: 59848

European-Finnish (FIN) AF: 0.776 AC: 16556 AN: 21332

Middle Eastern (MID) AF: 0.678 AC: 2738 AN: 4040

European-Non Finnish (NFE) AF: 0.682 AC: 590139 AN: 865496

Other (OTH) AF: 0.718 AC: 26498 AN: 36908

GnomAD4 genome AF: 0.718 AC: 108739 AN: 151362 Hom.: 39366 Cov.: 29 AF XY: 0.730 AC XY: 53983 AN XY: 73952

African (AFR) AF: 0.685 AC: 28238 AN: 41240

American (AMR) AF: 0.774 AC: 11772 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.745 AC: 2579 AN: 3464

East Asian (EAS) AF: 0.994 AC: 5128 AN: 5160

South Asian (SAS) AF: 0.835 AC: 4001 AN: 4794

European-Finnish (FIN) AF: 0.786 AC: 8149 AN: 10362

Middle Eastern (MID) AF: 0.705 AC: 206 AN: 292

European-Non Finnish (NFE) AF: 0.686 AC: 46537 AN: 67828

Other (OTH) AF: 0.705 AC: 1481 AN: 2100

Alfa AF: 0.608 Hom.: 1728

Bravo AF: 0.717

Asia WGS AF: 0.908 AC: 3153 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.48
DANN	Benign	0.43
PhyloP100		-0.98
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: rs7116739; hg19: chr11-35244044;