19-51265778-A-G

Variant names:

• chr19-51265778-A-G
• rs141713421
• NM_001385465.1:c.306A>G

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001385465.1(SIGLECL1):​c.306A>G​(p.Arg102Arg) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000452 in 1,614,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00043 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00045 (0 hom.)
• Consequence: SIGLECL1 NM_001385465.1 splice_region, synonymous
• Scores: Splicing: ADA: 0.001161
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.180

Genes affected

SIGLECL1 (HGNC:26856): (SIGLEC family like 1) Predicted to enable sialic acid binding activity. Predicted to be involved in cell adhesion. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000268595 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 19-51265778-A-G is Benign according to our data. Variant chr19-51265778-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2650369.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.18 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIGLECL1	NM_001385465.1	c.306A>G	p.Arg102Arg	splice_region_variant, synonymous_variant	Exon 4 of 6	ENST00000601727.6	NP_001372394.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIGLECL1	ENST00000601727.6	c.306A>G	p.Arg102Arg	splice_region_variant, synonymous_variant	Exon 4 of 6	3	NM_001385465.1	ENSP00000469601.2

Frequencies

GnomAD3 genomes AF: 0.000434 AC: 66 AN: 152206 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000691

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000517 AC: 130 AN: 251438 Hom.: 0 AF XY: 0.000449 AC XY: 61 AN XY: 135892

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.000173

Gnomad ASJ exome AF: 0.000198

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00176

Gnomad NFE exome AF: 0.000712

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000454 AC: 664 AN: 1461886 Hom.: 0 Cov.: 32 AF XY: 0.000458 AC XY: 333 AN XY: 727244

Gnomad4 AFR exome AF: 0.0000896

Gnomad4 AMR exome AF: 0.000335

Gnomad4 ASJ exome AF: 0.000115

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00174

Gnomad4 NFE exome AF: 0.000479

Gnomad4 OTH exome AF: 0.000248

GnomAD4 genome AF: 0.000433 AC: 66 AN: 152324 Hom.: 0 Cov.: 32 AF XY: 0.000389 AC XY: 29 AN XY: 74484

Gnomad4 AFR AF: 0.000120

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000941

Gnomad4 NFE AF: 0.000691

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000847 Hom.: 1

Bravo AF: 0.000442

EpiCase AF: 0.000763

EpiControl AF: 0.000889

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Mar 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SIGLECL1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.2
DANN	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0012
dbscSNV1_RF	Benign	0.040
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: rs141713421; hg19: chr19-51769032;