3-355870-A-G

Position:

• chr3-355870-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006614.4(CHL1):​c.1165+1099A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.88 in 152,142 control chromosomes in the GnomAD database, including 61,264 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.88 (61264 hom., cov: 32)
• Consequence: CHL1 NM_006614.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0810

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.988 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHL1	NM_006614.4	c.1165+1099A>G		intron_variant		ENST00000256509.7	NP_006605.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHL1	ENST00000256509.7	c.1165+1099A>G		intron_variant		1	NM_006614.4	ENSP00000256509	P3
CHL1	ENST00000397491.6	c.1117+1099A>G		intron_variant		1		ENSP00000380628
CHL1	ENST00000620033.4	c.1165+1099A>G		intron_variant		1		ENSP00000483512	A1
CHL1	ENST00000453040.5	c.*1455+1099A>G		intron_variant, NMD_transcript_variant		2		ENSP00000413109

Frequencies

GnomAD3 genomes AF: 0.880 AC: 133809 AN: 152024 Hom.: 61245 Cov.: 32

Gnomad AFR AF: 0.596

Gnomad AMI AF: 0.998

Gnomad AMR AF: 0.949

Gnomad ASJ AF: 0.995

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.976

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.953

Gnomad NFE AF: 0.994

Gnomad OTH AF: 0.916

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.880 AC: 133867 AN: 152142 Hom.: 61264 Cov.: 32 AF XY: 0.883 AC XY: 65679 AN XY: 74382

Gnomad4 AFR AF: 0.595

Gnomad4 AMR AF: 0.949

Gnomad4 ASJ AF: 0.995

Gnomad4 EAS AF: 0.994

Gnomad4 SAS AF: 0.976

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.994

Gnomad4 OTH AF: 0.917

Alfa AF: 0.939 Hom.: 15318

Bravo AF: 0.864

Asia WGS AF: 0.962 AC: 3347 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.4
DANN	Benign	0.42

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: rs892295; hg19: chr3-397553;