chr16-76427535-C-T

Variant names:

• chr16-76427535-C-T
• NM_033401.5:c.474C>T

Variant summary

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

The NM_033401.5(CNTNAP4):​c.474C>T​(p.Ile158Ile) variant causes a 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CNTNAP4 NM_033401.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.00
• Publications: 0 publications found

Genes affected

CNTNAP4 (HGNC:18747): (contactin associated protein family member 4) This gene encodes a member of the neurexin protein family. Members of this family function in the vertebrate nervous system as cell adhesion molecules and receptors. This protein contains epidermal growth factor repeats and laminin G domains. In addition, it includes an F5/8 type C domain, discoidin/neuropilin- and fibrinogen-like domains, and thrombospondin N-terminal-like domains. This protein may also play a role in proper neurotransmission in the dopaminergic and GABAergic systems and mutations in this gene may be associated with certain psychiatric illnesses. A polymorphism in an intron of this gene may be associated with longevity. [provided by RefSeq, Apr 2016]

ENSG00000287694 (HGNC:):

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 (BayesDel_noAF=-0.26).
• BP6: Variant 16-76427535-C-T is Benign according to our data. Variant chr16-76427535-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3146901.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033401.5. 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
	CNTNAP4	NM_033401.5	MANE Select	c.474C>T	p.Ile158Ile	synonymous	Exon 4 of 24	NP_207837.2	Q9C0A0-1
	CNTNAP4	NM_001322181.2		c.471C>T	p.Ile157Ile	synonymous	Exon 4 of 24	NP_001309110.1
	CNTNAP4	NM_001322188.2		c.474C>T	p.Ile158Ile	synonymous	Exon 4 of 25	NP_001309117.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTNAP4	ENST00000611870.5	TSL:1 MANE Select	c.474C>T	p.Ile158Ile	synonymous	Exon 4 of 24	ENSP00000479811.1	Q9C0A0-1
	CNTNAP4	ENST00000622250.4	TSL:1	c.474C>T	p.Ile158Ile	synonymous	Exon 4 of 23	ENSP00000477698.1	A0A087WTA1
	CNTNAP4	ENST00000463177.1	TSL:1	n.416C>T		non_coding_transcript_exon	Exon 4 of 5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	7.3
DANN	Benign	0.79
PhyloP100		-1.0

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

hg19: chr16-76461432;