NM_000610.4:c.*1664G>A

Variant names:

• chr11-35230997-G-A
• rs11821102
• NM_000610.4:c.*1664G>A

Variant summary

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

The NM_000610.4(CD44):​c.*1664G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0658 in 153,820 control chromosomes in the GnomAD database, including 487 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 0.066 (485 hom., cov: 32)
  • Exomes 𝑓: 0.033 (2 hom.)
• Consequence: CD44 NM_000610.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.39
• Publications: 21 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 = 0.137 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.*1664G>A		3_prime_UTR	Exon 18 of 18	NP_000601.3
	CD44	NM_001440324.1		c.*1664G>A		3_prime_UTR	Exon 18 of 18	NP_001427253.1
	CD44	NM_001440325.1		c.*1664G>A		3_prime_UTR	Exon 18 of 18	NP_001427254.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD44	ENST00000428726.8	TSL:1 MANE Select	c.*1664G>A		3_prime_UTR	Exon 18 of 18	ENSP00000398632.2
	CD44	ENST00000263398.11	TSL:1	c.*1664G>A		3_prime_UTR	Exon 9 of 9	ENSP00000263398.6

Frequencies

GnomAD3 genomes AF: 0.0661 AC: 10049 AN: 152058 Hom.: 482 Cov.: 32

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.0912

Gnomad AMR AF: 0.0308

Gnomad ASJ AF: 0.0170

Gnomad EAS AF: 0.0819

Gnomad SAS AF: 0.0350

Gnomad FIN AF: 0.0262

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0392

Gnomad OTH AF: 0.0575

GnomAD4 exome AF: 0.0328 AC: 54 AN: 1644 Hom.: 2 Cov.: 0 AF XY: 0.0301 AC XY: 27 AN XY: 898

African (AFR) AF: 0.150 AC: 3 AN: 20

American (AMR) AF: 0.00 AC: 0 AN: 20

Ashkenazi Jewish (ASJ) AF: 0.0294 AC: 1 AN: 34

East Asian (EAS) AF: 0.100 AC: 22 AN: 220

South Asian (SAS) AF: 0.00 AC: 0 AN: 6

European-Finnish (FIN) AF: 0.0185 AC: 9 AN: 486

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0227 AC: 18 AN: 794

Other (OTH) AF: 0.0156 AC: 1 AN: 64

GnomAD4 genome AF: 0.0662 AC: 10067 AN: 152176 Hom.: 485 Cov.: 32 AF XY: 0.0660 AC XY: 4915 AN XY: 74416

African (AFR) AF: 0.140 AC: 5791 AN: 41500

American (AMR) AF: 0.0306 AC: 468 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0170 AC: 59 AN: 3472

East Asian (EAS) AF: 0.0822 AC: 426 AN: 5180

South Asian (SAS) AF: 0.0345 AC: 166 AN: 4818

European-Finnish (FIN) AF: 0.0262 AC: 278 AN: 10610

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0392 AC: 2666 AN: 67998

Other (OTH) AF: 0.0569 AC: 120 AN: 2108

Alfa AF: 0.0485 Hom.: 798

Bravo AF: 0.0685

Asia WGS AF: 0.0730 AC: 252 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	5.1
DANN	Benign	0.50
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11821102; hg19: chr11-35252544;