chr3-205790-T-G

Position:

• chr3-205790-T-G

Variant summary

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

The NM_006614.4(CHL1):​c.-175+8727T>G 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 152,226 control chromosomes in the GnomAD database, including 1,648 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 0.13 (1648 hom., cov: 33)
• Consequence: CHL1 NM_006614.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.345

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHL1	NM_006614.4	c.-175+8727T>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.-175+8727T>G		intron_variant		1	NM_006614.4	ENSP00000256509	P3

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20090 AN: 152108 Hom.: 1646 Cov.: 33

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.0429

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0987

Gnomad OTH AF: 0.138

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

GnomAD4 genome AF: 0.132 AC: 20113 AN: 152226 Hom.: 1648 Cov.: 33 AF XY: 0.137 AC XY: 10231 AN XY: 74420

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.397

Gnomad4 SAS AF: 0.283

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.0987

Gnomad4 OTH AF: 0.138

Alfa AF: 0.107 Hom.: 567

Bravo AF: 0.134

Asia WGS AF: 0.339 AC: 1180 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.8
DANN	Benign	0.73

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: rs5024851; hg19: chr3-247473;