NM_001769.4:c.621+343C>A

Variant names:

• chr12-6236618-C-A
• rs3181301
• NM_001769.4:c.621+343C>A

Variant summary

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

The NM_001769.4(CD9):​c.621+343C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 420,900 control chromosomes in the GnomAD database, including 51,294 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 0.46 (16683 hom., cov: 33)
  • Exomes 𝑓: 0.50 (34611 hom.)
• Consequence: CD9 NM_001769.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0290
• Publications: 12 publications found

Genes affected

CD9 (HGNC:1709): (CD9 molecule) This gene encodes a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Tetraspanins are cell surface glycoproteins with four transmembrane domains that form multimeric complexes with other cell surface proteins. The encoded protein functions in many cellular processes including differentiation, adhesion, and signal transduction, and expression of this gene plays a critical role in the suppression of cancer cell motility and metastasis. [provided by RefSeq, Jan 2011]

ENSG00000305396 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001769.4. 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
	CD9	NM_001769.4	MANE Select	c.621+343C>A		intron	N/A	NP_001760.1
	CD9	NM_001413241.1		c.702+343C>A		intron	N/A	NP_001400170.1
	CD9	NM_001413242.1		c.690+343C>A		intron	N/A	NP_001400171.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD9	ENST00000009180.10	TSL:1 MANE Select	c.621+343C>A		intron	N/A	ENSP00000009180.4
	CD9	ENST00000677318.1		n.1726C>A		non_coding_transcript_exon	Exon 6 of 6
	CD9	ENST00000677572.1		n.*939C>A		non_coding_transcript_exon	Exon 6 of 7	ENSP00000503576.1

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70598 AN: 151996 Hom.: 16669 Cov.: 33

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.522

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.512

Gnomad OTH AF: 0.494

GnomAD4 exome AF: 0.504 AC: 135447 AN: 268784 Hom.: 34611 Cov.: 0 AF XY: 0.504 AC XY: 69111 AN XY: 137056

African (AFR) AF: 0.376 AC: 3032 AN: 8054

American (AMR) AF: 0.438 AC: 4250 AN: 9706

Ashkenazi Jewish (ASJ) AF: 0.597 AC: 5821 AN: 9746

East Asian (EAS) AF: 0.443 AC: 10673 AN: 24084

South Asian (SAS) AF: 0.472 AC: 2779 AN: 5886

European-Finnish (FIN) AF: 0.494 AC: 10529 AN: 21328

Middle Eastern (MID) AF: 0.644 AC: 883 AN: 1372

European-Non Finnish (NFE) AF: 0.518 AC: 88623 AN: 171224

Other (OTH) AF: 0.509 AC: 8857 AN: 17384

GnomAD4 genome AF: 0.464 AC: 70642 AN: 152116 Hom.: 16683 Cov.: 33 AF XY: 0.463 AC XY: 34430 AN XY: 74354

African (AFR) AF: 0.374 AC: 15532 AN: 41492

American (AMR) AF: 0.451 AC: 6903 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.596 AC: 2067 AN: 3470

East Asian (EAS) AF: 0.422 AC: 2176 AN: 5162

South Asian (SAS) AF: 0.469 AC: 2259 AN: 4816

European-Finnish (FIN) AF: 0.490 AC: 5189 AN: 10592

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.512 AC: 34829 AN: 67982

Other (OTH) AF: 0.497 AC: 1047 AN: 2106

Alfa AF: 0.483 Hom.: 9405

Bravo AF: 0.461

Asia WGS AF: 0.413 AC: 1437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.78
DANN	Benign	0.55
PhyloP100		0.029
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: rs3181301; hg19: chr12-6345784;