4-5748087-C-T

Variant names:

• chr4-5748087-C-T
• rs4688964
• NM_153717.3:c.940-61C>T

Variant summary

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

The NM_153717.3(EVC):​c.940-61C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 1,578,494 control chromosomes in the GnomAD database, including 17,709 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1946 hom., cov: 34)
  • Exomes 𝑓: 0.13 (15763 hom.)
• Consequence: EVC NM_153717.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.440
• Publications: 7 publications found

Genes affected

EVC (HGNC:3497): (EvC ciliary complex subunit 1) This gene encodes a protein containing a leucine zipper and a transmembrane domain. This gene has been implicated in both Ellis-van Creveld syndrome (EvC) and Weyers acrodental dysostosis. [provided by RefSeq, Jul 2008]

CRMP1 (HGNC:2365): (collapsin response mediator protein 1) This gene encodes a member of a family of cytosolic phosphoproteins expressed exclusively in the nervous system. The encoded protein is thought to be a part of the semaphorin signal transduction pathway implicated in semaphorin-induced growth cone collapse during neural development. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 4-5748087-C-T is Benign according to our data. Variant chr4-5748087-C-T is described in ClinVar as Benign. ClinVar VariationId is 1266411.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153717.3. 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
	EVC	NM_153717.3	MANE Select	c.940-61C>T		intron	N/A	NP_714928.1	P57679
	EVC	NM_001306090.2		c.940-61C>T		intron	N/A	NP_001293019.1
	EVC	NM_001306092.2		c.940-61C>T		intron	N/A	NP_001293021.1	E9PCN4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EVC	ENST00000264956.11	TSL:1 MANE Select	c.940-61C>T		intron	N/A	ENSP00000264956.6	P57679
	EVC	ENST00000509451.1	TSL:1	c.940-61C>T		intron	N/A	ENSP00000426774.1	E9PCN4
	EVC	ENST00000861182.1		c.940-61C>T		intron	N/A	ENSP00000531241.1

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22306 AN: 151960 Hom.: 1946 Cov.: 34

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.161

GnomAD4 exome AF: 0.130 AC: 185404 AN: 1426416 Hom.: 15763 Cov.: 26 AF XY: 0.133 AC XY: 94581 AN XY: 712020

African (AFR) AF: 0.153 AC: 5010 AN: 32678

American (AMR) AF: 0.237 AC: 10543 AN: 44540

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 4559 AN: 25842

East Asian (EAS) AF: 0.440 AC: 17370 AN: 39442

South Asian (SAS) AF: 0.224 AC: 19080 AN: 85040

European-Finnish (FIN) AF: 0.0949 AC: 4985 AN: 52516

Middle Eastern (MID) AF: 0.185 AC: 1048 AN: 5676

European-Non Finnish (NFE) AF: 0.106 AC: 114133 AN: 1081544

Other (OTH) AF: 0.147 AC: 8676 AN: 59138

GnomAD4 genome AF: 0.147 AC: 22320 AN: 152078 Hom.: 1946 Cov.: 34 AF XY: 0.151 AC XY: 11236 AN XY: 74340

African (AFR) AF: 0.153 AC: 6348 AN: 41464

American (AMR) AF: 0.200 AC: 3054 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 613 AN: 3470

East Asian (EAS) AF: 0.430 AC: 2210 AN: 5140

South Asian (SAS) AF: 0.230 AC: 1109 AN: 4814

European-Finnish (FIN) AF: 0.100 AC: 1061 AN: 10588

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7374 AN: 68004

Other (OTH) AF: 0.163 AC: 343 AN: 2110

Alfa AF: 0.123 Hom.: 1697

Bravo AF: 0.158

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	-0.80
CADD	Benign	3.8
DANN	Benign	0.75
PhyloP100		-0.44
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: rs4688964; hg19: chr4-5749814; COSMIC: COSV53839862; COSMIC: COSV53839862;