rs369473842

Variant names:

• chr11-35176644-G-A
• rs369473842
• NM_000610.4:c.137G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-35176644-G-A
• chr11-35176644-G-C

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP6

The NM_000610.4(CD44):​c.137G>A​(p.Arg46Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R46W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CD44 NM_000610.4 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.761
• Publications: 13 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19263604).
• BP6: Variant 11-35176644-G-A is Benign according to our data. Variant chr11-35176644-G-A is described in ClinVar as Benign. ClinVar VariationId is 599021.Status of the report is no_assertion_criteria_provided, 0 stars.

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.137G>A	p.Arg46Gln	missense	Exon 2 of 18	NP_000601.3
	CD44	NM_001440324.1		c.137G>A	p.Arg46Gln	missense	Exon 2 of 18	NP_001427253.1
	CD44	NM_001440325.1		c.137G>A	p.Arg46Gln	missense	Exon 2 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.137G>A	p.Arg46Gln	missense	Exon 2 of 18	ENSP00000398632.2	P16070-1
	CD44	ENST00000415148.6	TSL:1	c.137G>A	p.Arg46Gln	missense	Exon 2 of 17	ENSP00000389830.2	P16070-4
	CD44	ENST00000433892.6	TSL:1	c.137G>A	p.Arg46Gln	missense	Exon 2 of 12	ENSP00000392331.2	P16070-10

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251286 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461840 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727220

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111976

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	INDIAN BLOOD GROUP SYSTEM POLYMORPHISM (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.10	N
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.76
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.10
Sift	Benign	0.20	T
Sift4G	Benign	0.12	T
Polyphen		0.84	P
Vest4		0.25
MutPred		0.69		Loss of methylation at R46 (P = 0.0145)
MVP		0.29
MPC		1.7
ClinPred		0.74	D
GERP RS		1.7
PromoterAI		-0.014	Neutral
Varity_R		0.22
gMVP		0.78
Mutation Taster		=81/19	polymorphism

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: rs369473842; hg19: chr11-35198191;