11-35216912-A-G

Variant names:

• chr11-35216912-A-G
• rs1547059
• NM_000610.4:c.1873+1998A>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.1873+1998A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.722 in 152,144 control chromosomes in the GnomAD database, including 39,936 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 0.72 (39936 hom., cov: 32)
• Consequence: CD44 NM_000610.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.637
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.97 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.1873+1998A>G		intron	N/A	NP_000601.3
	CD44	NM_001440324.1		c.1876+1998A>G		intron	N/A	NP_001427253.1
	CD44	NM_001440325.1		c.1870+1998A>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.1873+1998A>G		intron	N/A	ENSP00000398632.2
	CD44	ENST00000415148.6	TSL:1	c.1744+1998A>G		intron	N/A	ENSP00000389830.2
	CD44	ENST00000433892.6	TSL:1	c.1126+1998A>G		intron	N/A	ENSP00000392331.2

Frequencies

GnomAD3 genomes AF: 0.722 AC: 109702 AN: 152026 Hom.: 39887 Cov.: 32

Gnomad AFR AF: 0.714

Gnomad AMI AF: 0.627

Gnomad AMR AF: 0.768

Gnomad ASJ AF: 0.712

Gnomad EAS AF: 0.993

Gnomad SAS AF: 0.817

Gnomad FIN AF: 0.762

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.684

Gnomad OTH AF: 0.711

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

GnomAD4 genome AF: 0.722 AC: 109809 AN: 152144 Hom.: 39936 Cov.: 32 AF XY: 0.732 AC XY: 54459 AN XY: 74386

African (AFR) AF: 0.714 AC: 29644 AN: 41498

American (AMR) AF: 0.769 AC: 11758 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.712 AC: 2472 AN: 3470

East Asian (EAS) AF: 0.993 AC: 5151 AN: 5188

South Asian (SAS) AF: 0.815 AC: 3928 AN: 4818

European-Finnish (FIN) AF: 0.762 AC: 8069 AN: 10588

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.684 AC: 46501 AN: 67970

Other (OTH) AF: 0.714 AC: 1511 AN: 2116

Alfa AF: 0.698 Hom.: 82344

Bravo AF: 0.722

Asia WGS AF: 0.897 AC: 3114 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.97
DANN	Benign	0.54
PhyloP100		-0.64
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: rs1547059; hg19: chr11-35238459;