NM_000610.4:c.68-10554T>C

Variant names:

• chr11-35166021-T-C
• rs353631
• NM_000610.4:c.68-10554T>C

Variant summary

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

The NM_000610.4(CD44):​c.68-10554T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 152,100 control chromosomes in the GnomAD database, including 4,974 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 0.25 (4974 hom., cov: 32)
• Consequence: CD44 NM_000610.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.673
• Publications: 3 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.283 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD44	NM_000610.4	MANE Select	c.68-10554T>C		intron	N/A	NP_000601.3
	CD44	NM_001440324.1		c.68-10554T>C		intron	N/A	NP_001427253.1
	CD44	NM_001440325.1		c.68-10554T>C		intron	N/A	NP_001427254.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD44	ENST00000428726.8	TSL:1 MANE Select	c.68-10554T>C		intron	N/A	ENSP00000398632.2
	CD44	ENST00000415148.6	TSL:1	c.68-10554T>C		intron	N/A	ENSP00000389830.2
	CD44	ENST00000433892.6	TSL:1	c.68-10554T>C		intron	N/A	ENSP00000392331.2

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38699 AN: 151982 Hom.: 4958 Cov.: 32

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.243

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

GnomAD4 genome AF: 0.255 AC: 38743 AN: 152100 Hom.: 4974 Cov.: 32 AF XY: 0.256 AC XY: 19036 AN XY: 74368

African (AFR) AF: 0.287 AC: 11909 AN: 41474

American (AMR) AF: 0.266 AC: 4058 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 561 AN: 3470

East Asian (EAS) AF: 0.121 AC: 627 AN: 5188

South Asian (SAS) AF: 0.230 AC: 1111 AN: 4830

European-Finnish (FIN) AF: 0.301 AC: 3182 AN: 10576

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.242 AC: 16473 AN: 67966

Other (OTH) AF: 0.249 AC: 526 AN: 2114

Alfa AF: 0.256 Hom.: 835

Bravo AF: 0.255

Asia WGS AF: 0.207 AC: 723 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.1
DANN	Benign	0.62
PhyloP100		-0.67
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: rs353631; hg19: chr11-35187568;