11-35222497-G-C

Position:

• chr11-35222497-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000428726.8(CD44):​c.2024+765G>C variant causes a intron 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 ENST00000428726.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.976

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD44	NM_000610.4	c.2024+765G>C		intron_variant		ENST00000428726.8	NP_000601.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD44	ENST00000428726.8	c.2024+765G>C		intron_variant		1	NM_000610.4	ENSP00000398632	A2

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

Gnomad4 AFR exome AF: 0.695

Gnomad4 AMR exome AF: 0.845

Gnomad4 ASJ exome AF: 0.738

Gnomad4 EAS exome AF: 0.997

Gnomad4 SAS exome AF: 0.823

Gnomad4 FIN exome AF: 0.776

Gnomad4 NFE exome AF: 0.682

Gnomad4 OTH exome AF: 0.718

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

Gnomad4 AFR AF: 0.685

Gnomad4 AMR AF: 0.774

Gnomad4 ASJ AF: 0.745

Gnomad4 EAS AF: 0.994

Gnomad4 SAS AF: 0.835

Gnomad4 FIN AF: 0.786

Gnomad4 NFE AF: 0.686

Gnomad4 OTH AF: 0.705

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.48
DANN	Benign	0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs7116739; hg19: chr11-35244044;