rs1244729864

Variant names:

• chr11-35189836-T-G
• rs1244729864
• NM_000610.4:c.438T>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_000610.4(CD44):​c.438T>G​(p.Thr146Thr) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CD44 NM_000610.4 splice_region, synonymous
• Scores: Splicing: ADA: 0.00009835
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.01
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.055).
• BP6: Variant 11-35189836-T-G is Benign according to our data. Variant chr11-35189836-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 756739.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.01 with no splicing effect.

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.438T>G	p.Thr146Thr	splice_region synonymous	Exon 5 of 18	NP_000601.3
	CD44	NM_001440324.1		c.438T>G	p.Thr146Thr	splice_region synonymous	Exon 5 of 18	NP_001427253.1
	CD44	NM_001440325.1		c.438T>G	p.Thr146Thr	splice_region synonymous	Exon 5 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.438T>G	p.Thr146Thr	splice_region synonymous	Exon 5 of 18	ENSP00000398632.2	P16070-1
	CD44	ENST00000415148.6	TSL:1	c.438T>G	p.Thr146Thr	splice_region synonymous	Exon 5 of 17	ENSP00000389830.2	P16070-4
	CD44	ENST00000433892.6	TSL:1	c.438T>G	p.Thr146Thr	splice_region synonymous	Exon 5 of 12	ENSP00000392331.2	P16070-10

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.0
DANN	Benign	0.47
PhyloP100		-1.0
PromoterAI		-0.013	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000098
dbscSNV1_RF	Benign	0.0020
SpliceAI score (max)		0.020		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: rs1244729864; hg19: chr11-35211383;