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

African (AFR) AF: 0.0818 AC: 2737 AN: 33454

American (AMR) AF: 0.426 AC: 19043 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 9694 AN: 26066

East Asian (EAS) AF: 0.352 AC: 13944 AN: 39634

South Asian (SAS) AF: 0.253 AC: 21735 AN: 86068

European-Finnish (FIN) AF: 0.488 AC: 25986 AN: 53304

Middle Eastern (MID) AF: 0.274 AC: 1575 AN: 5738

European-Non Finnish (NFE) AF: 0.421 AC: 466844 AN: 1108042

Other (OTH) 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

African (AFR) AF: 0.0961 AC: 3991 AN: 41514

American (AMR) AF: 0.402 AC: 6140 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 1191 AN: 3470

East Asian (EAS) AF: 0.389 AC: 2005 AN: 5156

South Asian (SAS) AF: 0.264 AC: 1271 AN: 4814

European-Finnish (FIN) AF: 0.486 AC: 5126 AN: 10554

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.416 AC: 28296 AN: 67966

Other (OTH) AF: 0.328 AC: 692 AN: 2112

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 22, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	9.0
DANN	Benign	0.68
PhyloP100		0.60
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

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Other links and lift over

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