3-111563017-C-T

Variant names:

• chr3-111563017-C-T
• rs1398748
• NM_005816.5:c.419-4506C>T

Variant summary

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

The NM_005816.5(CD96):​c.419-4506C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 152,094 control chromosomes in the GnomAD database, including 12,198 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 0.38 (12198 hom., cov: 33)
• Consequence: CD96 NM_005816.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305
• Publications: 7 publications found

Genes affected

CD96 (HGNC:16892): (CD96 molecule) The protein encoded by this gene belongs to the immunoglobulin superfamily. It is a type I membrane protein. The protein may play a role in the adhesive interactions of activated T and NK cells during the late phase of the immune response. It may also function in antigen presentation. Alternative splicing generates multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jan 2016]

CD96 Gene-Disease associations (from GenCC):

• C syndrome

  Inheritance: Unknown, AD, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005816.5. 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
	CD96	NM_005816.5	MANE Select	c.419-4506C>T		intron	N/A	NP_005807.1
	CD96	NM_198196.3		c.419-4506C>T		intron	N/A	NP_937839.1
	CD96	NM_001410800.1		c.419-4506C>T		intron	N/A	NP_001397729.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD96	ENST00000352690.9	TSL:1 MANE Select	c.419-4506C>T		intron	N/A	ENSP00000342040.3
	CD96	ENST00000283285.10	TSL:1	c.419-4506C>T		intron	N/A	ENSP00000283285.5
	CD96	ENST00000438817.6	TSL:1	c.419-4506C>T		intron	N/A	ENSP00000389801.2

Frequencies

GnomAD3 genomes AF: 0.375 AC: 57029 AN: 151976 Hom.: 12187 Cov.: 33

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.498

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.389

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.465

Gnomad OTH AF: 0.409

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

GnomAD4 genome AF: 0.375 AC: 57050 AN: 152094 Hom.: 12198 Cov.: 33 AF XY: 0.375 AC XY: 27847 AN XY: 74314

African (AFR) AF: 0.154 AC: 6395 AN: 41498

American (AMR) AF: 0.457 AC: 6992 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.498 AC: 1729 AN: 3472

East Asian (EAS) AF: 0.463 AC: 2396 AN: 5172

South Asian (SAS) AF: 0.506 AC: 2435 AN: 4816

European-Finnish (FIN) AF: 0.389 AC: 4107 AN: 10562

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.465 AC: 31580 AN: 67966

Other (OTH) AF: 0.412 AC: 872 AN: 2114

Alfa AF: 0.428 Hom.: 7081

Bravo AF: 0.366

Asia WGS AF: 0.473 AC: 1644 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.2
DANN	Benign	0.38
PhyloP100		0.30
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: rs1398748; hg19: chr3-111281864;