rs9666607

Variant names:

• chr11-35204608-A-G
• rs9666607
• NM_000610.4:c.1250A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-35204608-A-G
• chr11-35204608-A-C
• chr11-35204608-A-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_000610.4(CD44):​c.1250A>G​(p.Lys417Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.71 in 1,611,714 control chromosomes in the GnomAD database, including 410,458 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.76 (44325 hom., cov: 32)
  • Exomes 𝑓: 0.70 (366133 hom.)
• Consequence: CD44 NM_000610.4 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.466
• Publications: 55 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.028172E-7).
• BP6: Variant 11-35204608-A-G is Benign according to our data. Variant chr11-35204608-A-G is described in ClinVar as Benign. ClinVar VariationId is 3059515.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.906 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.1250A>G	p.Lys417Arg	missense	Exon 10 of 18	NP_000601.3
	CD44	NM_001440324.1		c.1253A>G	p.Lys418Arg	missense	Exon 10 of 18	NP_001427253.1
	CD44	NM_001440325.1		c.1250A>G	p.Lys417Arg	missense	Exon 10 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.1250A>G	p.Lys417Arg	missense	Exon 10 of 18	ENSP00000398632.2	P16070-1
	CD44	ENST00000415148.6	TSL:1	c.1121A>G	p.Lys374Arg	missense	Exon 9 of 17	ENSP00000389830.2	P16070-4
	CD44	ENST00000433892.6	TSL:1	c.668-3497A>G		intron	N/A	ENSP00000392331.2	P16070-10

Frequencies

GnomAD3 genomes AF: 0.758 AC: 115177 AN: 152030 Hom.: 44275 Cov.: 32

Gnomad AFR AF: 0.879

Gnomad AMI AF: 0.655

Gnomad AMR AF: 0.703

Gnomad ASJ AF: 0.776

Gnomad EAS AF: 0.928

Gnomad SAS AF: 0.826

Gnomad FIN AF: 0.744

Gnomad MID AF: 0.736

Gnomad NFE AF: 0.681

Gnomad OTH AF: 0.749

GnomAD2 exomes AF: 0.741 AC: 186203 AN: 251120 AF XY: 0.741

Gnomad AFR exome AF: 0.881

Gnomad AMR exome AF: 0.682

Gnomad ASJ exome AF: 0.769

Gnomad EAS exome AF: 0.926

Gnomad FIN exome AF: 0.734

Gnomad NFE exome AF: 0.689

Gnomad OTH exome AF: 0.726

GnomAD4 exome AF: 0.705 AC: 1028972 AN: 1459564 Hom.: 366133 Cov.: 37 AF XY: 0.708 AC XY: 514030 AN XY: 726236

African (AFR) AF: 0.882 AC: 29493 AN: 33420

American (AMR) AF: 0.685 AC: 30596 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.767 AC: 20018 AN: 26090

East Asian (EAS) AF: 0.943 AC: 37391 AN: 39670

South Asian (SAS) AF: 0.821 AC: 70775 AN: 86218

European-Finnish (FIN) AF: 0.730 AC: 38963 AN: 53396

Middle Eastern (MID) AF: 0.712 AC: 4102 AN: 5758

European-Non Finnish (NFE) AF: 0.679 AC: 754252 AN: 1110034

Other (OTH) AF: 0.719 AC: 43382 AN: 60296

GnomAD4 genome AF: 0.758 AC: 115284 AN: 152150 Hom.: 44325 Cov.: 32 AF XY: 0.764 AC XY: 56834 AN XY: 74370

African (AFR) AF: 0.879 AC: 36513 AN: 41528

American (AMR) AF: 0.703 AC: 10744 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.776 AC: 2696 AN: 3472

East Asian (EAS) AF: 0.928 AC: 4802 AN: 5176

South Asian (SAS) AF: 0.825 AC: 3973 AN: 4816

European-Finnish (FIN) AF: 0.744 AC: 7873 AN: 10578

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.681 AC: 46284 AN: 67974

Other (OTH) AF: 0.751 AC: 1589 AN: 2116

Alfa AF: 0.715 Hom.: 104117

Bravo AF: 0.760

TwinsUK AF: 0.690 AC: 2559

ALSPAC AF: 0.674 AC: 2597

ESP6500AA AF: 0.867 AC: 3820

ESP6500EA AF: 0.693 AC: 5961

ExAC AF: 0.748 AC: 90765

Asia WGS AF: 0.874 AC: 3039 AN: 3478

EpiCase AF: 0.684

EpiControl AF: 0.682

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	CD44-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	4.1
DANN	Benign	0.58
DEOGEN2	Benign	0.23	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.060	N
LIST_S2	Benign	0.22	T
MetaRNN	Benign	7.0e-7	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.23	N
PhyloP100		0.47
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.030	N
REVEL	Benign	0.028
Sift	Benign	0.89	T
Sift4G	Benign	0.38	T
Polyphen		0.0	B
Vest4		0.0080
MPC		0.038
ClinPred		0.00040	T
GERP RS		1.9
Varity_R		0.026
gMVP		0.066
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs9666607; hg19: chr11-35226155; COSMIC: COSV53530507; COSMIC: COSV53530507;