3-340846-A-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_006614.4(CHL1):c.438A>C(p.Gly146=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00106 in 1,611,886 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00070 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (5 hom.)
• Consequence: CHL1 NM_006614.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.26

Genes affected

CHL1 (HGNC:1939): (cell adhesion molecule L1 like) The protein encoded by this gene is a member of the L1 gene family of neural cell adhesion molecules. It is a neural recognition molecule that may be involved in signal transduction pathways. The deletion of one copy of this gene may be responsible for mental defects in patients with 3p- syndrome. This protein may also play a role in the growth of certain cancers. Alternate splicing results in both coding and non-coding variants. [provided by RefSeq, Nov 2011]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 3-340846-A-C is Benign according to our data. Variant chr3-340846-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 787658.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.26 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHL1	NM_006614.4	c.438A>C	p.Gly146=	synonymous_variant	6/28	ENST00000256509.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHL1	ENST00000256509.7	c.438A>C	p.Gly146=	synonymous_variant	6/28	1	NM_006614.4	P3

Frequencies

GnomAD3 genomes AF: 0.000704 AC: 107 AN: 152086 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000590

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00125

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000972 AC: 244 AN: 250920 Hom.: 3 AF XY: 0.00104 AC XY: 141 AN XY: 135646

Gnomad AFR exome AF: 0.0000617

Gnomad AMR exome AF: 0.000493

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00154

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00153

Gnomad OTH exome AF: 0.000817

GnomAD4 exome AF: 0.00110 AC: 1606 AN: 1459682 Hom.: 5 Cov.: 30 AF XY: 0.00113 AC XY: 822 AN XY: 726276

Gnomad4 AFR exome AF: 0.0000897

Gnomad4 AMR exome AF: 0.000403

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00166

Gnomad4 FIN exome AF: 0.000150

Gnomad4 NFE exome AF: 0.00125

Gnomad4 OTH exome AF: 0.000663

GnomAD4 genome AF: 0.000703 AC: 107 AN: 152204 Hom.: 0 Cov.: 33 AF XY: 0.000538 AC XY: 40 AN XY: 74416

Gnomad4 AFR AF: 0.000217

Gnomad4 AMR AF: 0.000589

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000623

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.00125

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00110 Hom.: 0

Bravo AF: 0.000790

EpiCase AF: 0.00191

EpiControl AF: 0.00130

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.70
Dann	Benign	0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs148439738; hg19: chr3-382529;