rs112762

Variant names:

• chr11-35171082-C-T
• rs112762
• NM_000610.4:c.68-5493C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-35171082-C-T
• chr11-35171082-C-G

Variant summary

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

The NM_000610.4(CD44):​c.68-5493C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 152,048 control chromosomes in the GnomAD database, including 24,487 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: 𝑓 0.56 (24487 hom., cov: 33)
• Consequence: CD44 NM_000610.4 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -0.163
• Publications: 7 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.691 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.68-5493C>T		intron	N/A	NP_000601.3
	CD44	NM_001440324.1		c.68-5493C>T		intron	N/A	NP_001427253.1
	CD44	NM_001440325.1		c.68-5493C>T		intron	N/A	NP_001427254.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD44	ENST00000428726.8	TSL:1 MANE Select	c.68-5493C>T		intron	N/A	ENSP00000398632.2	P16070-1
	CD44	ENST00000415148.6	TSL:1	c.68-5493C>T		intron	N/A	ENSP00000389830.2	P16070-4
	CD44	ENST00000433892.6	TSL:1	c.68-5493C>T		intron	N/A	ENSP00000392331.2	P16070-10

Frequencies

GnomAD3 genomes AF: 0.557 AC: 84564 AN: 151930 Hom.: 24435 Cov.: 33

Gnomad AFR AF: 0.697

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.587

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.566

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

GnomAD4 genome AF: 0.557 AC: 84686 AN: 152048 Hom.: 24487 Cov.: 33 AF XY: 0.554 AC XY: 41180 AN XY: 74362

African (AFR) AF: 0.698 AC: 28921 AN: 41462

American (AMR) AF: 0.588 AC: 8985 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.517 AC: 1791 AN: 3466

East Asian (EAS) AF: 0.307 AC: 1591 AN: 5174

South Asian (SAS) AF: 0.538 AC: 2592 AN: 4818

European-Finnish (FIN) AF: 0.440 AC: 4647 AN: 10566

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.505 AC: 34324 AN: 67958

Other (OTH) AF: 0.568 AC: 1200 AN: 2112

Alfa AF: 0.448 Hom.: 1805

Bravo AF: 0.570

Asia WGS AF: 0.465 AC: 1616 AN: 3478

ClinVar

ClinVar submissions

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	-0.88
CADD	Benign	1.1
DANN	Benign	0.35
PhyloP100		-0.16
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs112762;

hg19: chr11-35192629;