chr3-3042759-A-T

Variant names:

• chr3-3042759-A-T
• rs468314
• NM_175607.3:c.2512-218A>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_175607.3(CNTN4):​c.2512-218A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 605,162 control chromosomes in the GnomAD database, including 5,658 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (2888 hom., cov: 33)
  • Exomes 𝑓: 0.096 (2770 hom.)
• Consequence: CNTN4 NM_175607.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.683
• Publications: 0 publications found

Genes affected

CNTN4 (HGNC:2174): (contactin 4) This gene encodes a member of the contactin family of immunoglobulins. Contactins are axon-associated cell adhesion molecules that function in neuronal network formation and plasticity. The encoded protein is a glycosylphosphatidylinositol-anchored neuronal membrane protein that may play a role in the formation of axon connections in the developing nervous system. Deletion or mutation of this gene may play a role in 3p deletion syndrome and autism spectrum disorders. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2011]

CNTN4-AS1 (HGNC:39985): (CNTN4 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 3-3042759-A-T is Benign according to our data. Variant chr3-3042759-A-T is described in ClinVar as Benign. ClinVar VariationId is 1287127.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175607.3. 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
	CNTN4	NM_175607.3	MANE Select	c.2512-218A>T		intron	N/A	NP_783200.1	Q8IWV2-1
	CNTN4	NM_001206955.2		c.2512-218A>T		intron	N/A	NP_001193884.1	Q8IWV2-1
	CNTN4	NM_001350095.2		c.2512-218A>T		intron	N/A	NP_001337024.1	Q8IWV2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTN4	ENST00000418658.6	TSL:5 MANE Select	c.2512-218A>T		intron	N/A	ENSP00000396010.1	Q8IWV2-1
	CNTN4	ENST00000397459.6	TSL:1	c.1528-218A>T		intron	N/A	ENSP00000380600.2	Q8IWV2-4
	CNTN4	ENST00000484686.1	TSL:1	n.762-218A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24143 AN: 152024 Hom.: 2871 Cov.: 33

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0643

Gnomad FIN AF: 0.0523

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.0982

Gnomad OTH AF: 0.149

GnomAD4 exome AF: 0.0961 AC: 43546 AN: 453020 Hom.: 2770 AF XY: 0.0947 AC XY: 22820 AN XY: 241028

African (AFR) AF: 0.336 AC: 4179 AN: 12444

American (AMR) AF: 0.0911 AC: 1693 AN: 18588

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 2443 AN: 13706

East Asian (EAS) AF: 0.000484 AC: 15 AN: 30980

South Asian (SAS) AF: 0.0721 AC: 3207 AN: 44466

European-Finnish (FIN) AF: 0.0541 AC: 1619 AN: 29900

Middle Eastern (MID) AF: 0.145 AC: 286 AN: 1978

European-Non Finnish (NFE) AF: 0.0989 AC: 27180 AN: 274860

Other (OTH) AF: 0.112 AC: 2924 AN: 26098

GnomAD4 genome AF: 0.159 AC: 24193 AN: 152142 Hom.: 2888 Cov.: 33 AF XY: 0.153 AC XY: 11414 AN XY: 74400

African (AFR) AF: 0.335 AC: 13872 AN: 41446

American (AMR) AF: 0.118 AC: 1802 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 549 AN: 3468

East Asian (EAS) AF: 0.00173 AC: 9 AN: 5188

South Asian (SAS) AF: 0.0648 AC: 312 AN: 4818

European-Finnish (FIN) AF: 0.0523 AC: 555 AN: 10610

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.0982 AC: 6680 AN: 67998

Other (OTH) AF: 0.147 AC: 311 AN: 2116

Alfa AF: 0.137 Hom.: 252

Bravo AF: 0.172

Asia WGS AF: 0.0480 AC: 167 AN: 3478

ClinVar

ClinVar submissions

Significance: 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	-0.81
CADD	Benign	4.3
DANN	Benign	0.47
PhyloP100		0.68
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: rs468314; hg19: chr3-3084443;