chr3-3040341-G-T

Variant names:

• chr3-3040341-G-T
• rs4685596
• NM_175607.3:c.2398+70G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_175607.3(CNTN4):​c.2398+70G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 1,159,798 control chromosomes in the GnomAD database, including 35,995 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (5238 hom., cov: 34)
  • Exomes 𝑓: 0.24 (30757 hom.)
• Consequence: CNTN4 NM_175607.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.09
• Publications: 4 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 3-3040341-G-T is Benign according to our data. Variant chr3-3040341-G-T is described in ClinVar as Benign. ClinVar VariationId is 1288739.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.291 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.2398+70G>T		intron	N/A	NP_783200.1	Q8IWV2-1
	CNTN4	NM_001206955.2		c.2398+70G>T		intron	N/A	NP_001193884.1	Q8IWV2-1
	CNTN4	NM_001350095.2		c.2398+70G>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.2398+70G>T		intron	N/A	ENSP00000396010.1	Q8IWV2-1
	CNTN4	ENST00000397459.6	TSL:1	c.1414+70G>T		intron	N/A	ENSP00000380600.2	Q8IWV2-4
	CNTN4	ENST00000484686.1	TSL:1	n.648+70G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38928 AN: 152046 Hom.: 5222 Cov.: 34

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.272

GnomAD4 exome AF: 0.243 AC: 244939 AN: 1007634 Hom.: 30757 Cov.: 13 AF XY: 0.242 AC XY: 125421 AN XY: 518490

African (AFR) AF: 0.301 AC: 7509 AN: 24964

American (AMR) AF: 0.197 AC: 8099 AN: 41196

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 6972 AN: 23120

East Asian (EAS) AF: 0.141 AC: 5243 AN: 37294

South Asian (SAS) AF: 0.195 AC: 14799 AN: 75700

European-Finnish (FIN) AF: 0.212 AC: 9939 AN: 46960

Middle Eastern (MID) AF: 0.319 AC: 1447 AN: 4534

European-Non Finnish (NFE) AF: 0.253 AC: 179311 AN: 708158

Other (OTH) AF: 0.254 AC: 11620 AN: 45708

GnomAD4 genome AF: 0.256 AC: 38973 AN: 152164 Hom.: 5238 Cov.: 34 AF XY: 0.252 AC XY: 18742 AN XY: 74386

African (AFR) AF: 0.295 AC: 12252 AN: 41526

American (AMR) AF: 0.234 AC: 3585 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.308 AC: 1070 AN: 3472

East Asian (EAS) AF: 0.128 AC: 660 AN: 5172

South Asian (SAS) AF: 0.182 AC: 877 AN: 4820

European-Finnish (FIN) AF: 0.211 AC: 2230 AN: 10588

Middle Eastern (MID) AF: 0.346 AC: 101 AN: 292

European-Non Finnish (NFE) AF: 0.255 AC: 17317 AN: 67978

Other (OTH) AF: 0.275 AC: 581 AN: 2112

Alfa AF: 0.168 Hom.: 381

Bravo AF: 0.262

Asia WGS AF: 0.162 AC: 562 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.76
DANN	Benign	0.53
PhyloP100		-1.1
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: rs4685596; hg19: chr3-3082025;