3-319864-T-G

Position:

• chr3-319864-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000256509.7(CHL1):​c.88T>G​(p.Ser30Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00205 in 1,559,796 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0089 (19 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (25 hom.)
• Consequence: CHL1 ENST00000256509.7 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.38

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0055780113).
• BP6: Variant 3-319864-T-G is Benign according to our data. Variant chr3-319864-T-G is described in ClinVar as [Benign]. Clinvar id is 767882.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00894 (1360/152136) while in subpopulation AFR AF= 0.03 (1245/41546). AF 95% confidence interval is 0.0286. There are 19 homozygotes in gnomad4. There are 656 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHL1	NM_006614.4	c.88T>G	p.Ser30Ala	missense_variant	3/28	ENST00000256509.7	NP_006605.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHL1	ENST00000256509.7	c.88T>G	p.Ser30Ala	missense_variant	3/28	1	NM_006614.4	ENSP00000256509	P3

Frequencies

GnomAD3 genomes AF: 0.00885 AC: 1345 AN: 152018 Hom.: 19 Cov.: 32

Gnomad AFR AF: 0.0297

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00276

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00271

Gnomad SAS AF: 0.00808

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00527

GnomAD3 exomes AF: 0.00289 AC: 706 AN: 243914 Hom.: 9 AF XY: 0.00279 AC XY: 368 AN XY: 131956

Gnomad AFR exome AF: 0.0277

Gnomad AMR exome AF: 0.00110

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00193

Gnomad SAS exome AF: 0.00655

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000815

Gnomad OTH exome AF: 0.000841

GnomAD4 exome AF: 0.00130 AC: 1834 AN: 1407660 Hom.: 25 Cov.: 23 AF XY: 0.00140 AC XY: 983 AN XY: 703088

Gnomad4 AFR exome AF: 0.0304

Gnomad4 AMR exome AF: 0.00125

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00420

Gnomad4 SAS exome AF: 0.00587

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000291

Gnomad4 OTH exome AF: 0.00209

GnomAD4 genome AF: 0.00894 AC: 1360 AN: 152136 Hom.: 19 Cov.: 32 AF XY: 0.00882 AC XY: 656 AN XY: 74362

Gnomad4 AFR AF: 0.0300

Gnomad4 AMR AF: 0.00275

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00271

Gnomad4 SAS AF: 0.00830

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00521

Alfa AF: 0.00102 Hom.: 2

Bravo AF: 0.00984

ESP6500AA AF: 0.0234 AC: 103

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00361 AC: 437

Asia WGS AF: 0.00808 AC: 28 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.064	.;T;.;.;.;T;.
Eigen	Benign	-0.16
Eigen_PC	Benign	0.052
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.56	T;T;T;T;T;T;T
MetaRNN	Benign	0.0056	T;T;T;T;T;T;T
MetaSVM	Benign	-0.91	T
MutationTaster	Benign	0.50	N;N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.4	N;N;N;N;N;N;.
REVEL	Benign	0.12
Sift	Benign	0.055	T;T;T;T;T;T;.
Sift4G	Benign	0.58	T;T;T;T;T;T;T
Polyphen		0.035	B;B;.;.;.;.;.
Vest4		0.44
MVP		0.65
MPC		0.012
ClinPred		0.0090	T
GERP RS		4.9
Varity_R		0.16
gMVP		0.17

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: rs116261368; hg19: chr3-361547;