11-35228123-A-G

Variant names:

• chr11-35228123-A-G
• rs12419062
• NM_000610.4:c.2025-1006A>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.2025-1006A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 152,006 control chromosomes in the GnomAD database, including 16,693 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 0.44 (16693 hom., cov: 32)
• Consequence: CD44 NM_000610.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.45
• 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.658 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.2025-1006A>G		intron	N/A	NP_000601.3
	CD44	NM_001440324.1		c.2028-1006A>G		intron	N/A	NP_001427253.1
	CD44	NM_001440325.1		c.2022-1006A>G		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.2025-1006A>G		intron	N/A	ENSP00000398632.2
	CD44	ENST00000415148.6	TSL:1	c.1896-1006A>G		intron	N/A	ENSP00000389830.2
	CD44	ENST00000433892.6	TSL:1	c.1278-1006A>G		intron	N/A	ENSP00000392331.2

Frequencies

GnomAD3 genomes AF: 0.444 AC: 67461 AN: 151890 Hom.: 16656 Cov.: 32

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.491

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.437

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

GnomAD4 genome AF: 0.444 AC: 67566 AN: 152006 Hom.: 16693 Cov.: 32 AF XY: 0.442 AC XY: 32855 AN XY: 74276

African (AFR) AF: 0.664 AC: 27525 AN: 41434

American (AMR) AF: 0.491 AC: 7498 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1277 AN: 3466

East Asian (EAS) AF: 0.409 AC: 2113 AN: 5160

South Asian (SAS) AF: 0.242 AC: 1167 AN: 4814

European-Finnish (FIN) AF: 0.374 AC: 3954 AN: 10568

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.335 AC: 22770 AN: 67980

Other (OTH) AF: 0.441 AC: 932 AN: 2112

Alfa AF: 0.378 Hom.: 35130

Bravo AF: 0.467

Asia WGS AF: 0.378 AC: 1316 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.0040
DANN	Benign	0.65
PhyloP100		-5.5
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: rs12419062; hg19: chr11-35249670;