16-76461945-C-A

Variant names:

• chr16-76461945-C-A
• rs35994137
• NM_033401.5:c.1334-11C>A

Variant summary

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

The NM_033401.5(CNTNAP4):​c.1334-11C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 1,609,258 control chromosomes in the GnomAD database, including 130,391 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (9461 hom., cov: 31)
  • Exomes 𝑓: 0.40 (120930 hom.)
• Consequence: CNTNAP4 NM_033401.5 intron
• Scores: Splicing: ADA: 0.006034
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.600

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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 16-76461945-C-A is Benign according to our data. Variant chr16-76461945-C-A is described in ClinVar as [Benign]. Clinvar id is 1221600.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTNAP4	NM_033401.5	c.1334-11C>A		intron_variant	Intron 8 of 23	ENST00000611870.5	NP_207837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTNAP4	ENST00000611870.5	c.1334-11C>A		intron_variant	Intron 8 of 23	1	NM_033401.5	ENSP00000479811.1
ENSG00000287694	ENST00000655556.1	n.1334-11C>A		intron_variant	Intron 8 of 24			ENSP00000499374.1

Frequencies

GnomAD3 genomes AF: 0.323 AC: 49140 AN: 151936 Hom.: 9453 Cov.: 31

Gnomad AFR AF: 0.0963

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.389

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.486

Gnomad MID AF: 0.331

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.331

GnomAD2 exomes AF: 0.376 AC: 94403 AN: 250784 AF XY: 0.373

Gnomad AFR exome AF: 0.0871

Gnomad AMR exome AF: 0.430

Gnomad ASJ exome AF: 0.370

Gnomad EAS exome AF: 0.387

Gnomad FIN exome AF: 0.495

Gnomad NFE exome AF: 0.413

Gnomad OTH exome AF: 0.375

GnomAD4 exome AF: 0.401 AC: 583797 AN: 1457202 Hom.: 120930 Cov.: 31 AF XY: 0.397 AC XY: 287759 AN XY: 725146

Gnomad4 AFR exome AF: 0.0818 AC: 2737 AN: 33454

Gnomad4 AMR exome AF: 0.426 AC: 19043 AN: 44696

Gnomad4 ASJ exome AF: 0.372 AC: 9694 AN: 26066

Gnomad4 EAS exome AF: 0.352 AC: 13944 AN: 39634

Gnomad4 SAS exome AF: 0.253 AC: 21735 AN: 86068

Gnomad4 FIN exome AF: 0.488 AC: 25986 AN: 53304

Gnomad4 NFE exome AF: 0.421 AC: 466844 AN: 1108042

Gnomad4 Remaining exome AF: 0.369 AC: 22239 AN: 60200

GnomAD4 genome AF: 0.323 AC: 49163 AN: 152056 Hom.: 9461 Cov.: 31 AF XY: 0.327 AC XY: 24262 AN XY: 74308

Gnomad4 AFR AF: 0.0961 AC: 0.0961362 AN: 0.0961362

Gnomad4 AMR AF: 0.402 AC: 0.402254 AN: 0.402254

Gnomad4 ASJ AF: 0.343 AC: 0.343228 AN: 0.343228

Gnomad4 EAS AF: 0.389 AC: 0.388867 AN: 0.388867

Gnomad4 SAS AF: 0.264 AC: 0.264022 AN: 0.264022

Gnomad4 FIN AF: 0.486 AC: 0.485693 AN: 0.485693

Gnomad4 NFE AF: 0.416 AC: 0.416326 AN: 0.416326

Gnomad4 OTH AF: 0.328 AC: 0.327652 AN: 0.327652

Alfa AF: 0.297 Hom.: 1286

Bravo AF: 0.311

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Feb 22, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	9.0
DANN	Benign	0.68
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0060
dbscSNV1_RF	Benign	0.028
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs35994137; hg19: chr16-76495842; COSMIC: COSV56683009;