chr11-35222511-A-G

Variant names:

• chr11-35222511-A-G
• rs7116432
• ENST00000442151.6:c.*133A>G

Variant summary

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

The ENST00000428726.8(CD44):​c.2024+779A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 1,097,788 control chromosomes in the GnomAD database, including 71,016 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency:
  • Genomes: 𝑓 0.35 (10262 hom., cov: 29)
  • Exomes 𝑓: 0.35 (60754 hom.)
• Consequence: CD44 ENST00000428726.8 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -0.322
• Publications: 24 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.795 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000428726.8. 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+779A>G		intron	N/A	NP_000601.3
	CD44	NM_001202557.2		c.*133A>G		3_prime_UTR	Exon 9 of 9	NP_001189486.1
	CD44	NM_001440324.1		c.2027+779A>G		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.*133A>G		3_prime_UTR	Exon 9 of 9	ENSP00000398099.2
	CD44	ENST00000428726.8	TSL:1 MANE Select	c.2024+779A>G		intron	N/A	ENSP00000398632.2
	CD44	ENST00000415148.6	TSL:1	c.1895+779A>G		intron	N/A	ENSP00000389830.2

Frequencies

GnomAD3 genomes AF: 0.349 AC: 52685 AN: 151064 Hom.: 10267 Cov.: 29

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.440

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.416

Gnomad EAS AF: 0.816

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.350

GnomAD4 exome AF: 0.351 AC: 332511 AN: 946626 Hom.: 60754 Cov.: 19 AF XY: 0.355 AC XY: 160490 AN XY: 452076

African (AFR) AF: 0.222 AC: 3969 AN: 17864

American (AMR) AF: 0.507 AC: 3504 AN: 6914

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 3813 AN: 9314

East Asian (EAS) AF: 0.820 AC: 5675 AN: 6920

South Asian (SAS) AF: 0.533 AC: 21529 AN: 40420

European-Finnish (FIN) AF: 0.344 AC: 5254 AN: 15260

Middle Eastern (MID) AF: 0.309 AC: 1144 AN: 3704

European-Non Finnish (NFE) AF: 0.338 AC: 275329 AN: 813744

Other (OTH) AF: 0.378 AC: 12294 AN: 32486

GnomAD4 genome AF: 0.349 AC: 52685 AN: 151162 Hom.: 10262 Cov.: 29 AF XY: 0.359 AC XY: 26519 AN XY: 73834

African (AFR) AF: 0.235 AC: 9686 AN: 41248

American (AMR) AF: 0.432 AC: 6564 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.416 AC: 1442 AN: 3466

East Asian (EAS) AF: 0.815 AC: 4185 AN: 5132

South Asian (SAS) AF: 0.558 AC: 2671 AN: 4786

European-Finnish (FIN) AF: 0.332 AC: 3398 AN: 10250

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.347 AC: 23525 AN: 67802

Other (OTH) AF: 0.348 AC: 725 AN: 2086

Alfa AF: 0.342 Hom.: 11829

Bravo AF: 0.350

Asia WGS AF: 0.594 AC: 2059 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: association

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Nephrolithiasis, calcium oxalate (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.76
PhyloP100		-0.32
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: rs7116432; hg19: chr11-35244058; COSMIC: COSV53530497; COSMIC: COSV53530497;