chr19-51527908-A-G

Position:

• chr19-51527908-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001245.7(SIGLEC6):​c.1107-80T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.599 in 1,382,944 control chromosomes in the GnomAD database, including 249,138 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 0.60 (27660 hom., cov: 31)
  • Exomes 𝑓: 0.60 (221478 hom.)
• Consequence: SIGLEC6 NM_001245.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50

Genes affected

SIGLEC6 (HGNC:10875): (sialic acid binding Ig like lectin 6) This gene encodes a member of the SIGLEC (sialic acid binding immunoglobulin-like lectin) family of proteins. The encoded transmembrane receptor binds sialyl-TN glycans and leptin. Placental expression of the encoded protein is upregulated in preeclampsia. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIGLEC6	NM_001245.7	c.1107-80T>C		intron_variant		ENST00000425629.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIGLEC6	ENST00000425629.8	c.1107-80T>C		intron_variant		2	NM_001245.7	P2

Frequencies

GnomAD3 genomes AF: 0.601 AC: 91265 AN: 151858 Hom.: 27641 Cov.: 31

Gnomad AFR AF: 0.610

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.663

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.641

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.597

Gnomad OTH AF: 0.606

GnomAD4 exome AF: 0.598 AC: 736410 AN: 1230966 Hom.: 221478 AF XY: 0.598 AC XY: 372111 AN XY: 622642

Gnomad4 AFR exome AF: 0.600

Gnomad4 AMR exome AF: 0.718

Gnomad4 ASJ exome AF: 0.498

Gnomad4 EAS exome AF: 0.448

Gnomad4 SAS exome AF: 0.623

Gnomad4 FIN exome AF: 0.608

Gnomad4 NFE exome AF: 0.600

Gnomad4 OTH exome AF: 0.589

GnomAD4 genome AF: 0.601 AC: 91299 AN: 151978 Hom.: 27660 Cov.: 31 AF XY: 0.600 AC XY: 44581 AN XY: 74286

Gnomad4 AFR AF: 0.610

Gnomad4 AMR AF: 0.663

Gnomad4 ASJ AF: 0.490

Gnomad4 EAS AF: 0.452

Gnomad4 SAS AF: 0.641

Gnomad4 FIN AF: 0.607

Gnomad4 NFE AF: 0.597

Gnomad4 OTH AF: 0.597

Alfa AF: 0.590 Hom.: 5434

Bravo AF: 0.605

Asia WGS AF: 0.565 AC: 1964 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	5.3
DANN	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.26		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.26		Position offset: -3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs897783; hg19: chr19-52031162; COSMIC: COSV58432819; COSMIC: COSV58432819;