rs17701662

Variant names:

• chr20-3689865-A-T
• rs17701662
• NM_023068.4:c.4894+97T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_023068.4(SIGLEC1):​c.4894+97T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0546 in 1,215,546 control chromosomes in the GnomAD database, including 2,163 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 0.043 (208 hom., cov: 33)
  • Exomes 𝑓: 0.056 (1955 hom.)
• Consequence: SIGLEC1 NM_023068.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.493
• Publications: 4 publications found

Genes affected

SIGLEC1 (HGNC:11127): (sialic acid binding Ig like lectin 1) This gene encodes a member of the immunoglobulin superfamily. The encoded protein is a lectin-like adhesion molecule that binds glycoconjugate ligands on cell surfaces in a sialic acid-dependent manner. It is a type I transmembrane protein expressed only by a subpopulation of macrophages and is involved in mediating cell-cell interactions. The protein plays an important role in multiple human diseases and bacterial and viral infections has been shown to enhance SARS-CoV-2 infection. [provided by RefSeq, Dec 2021]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.064 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023068.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIGLEC1	NM_023068.4	MANE Select	c.4894+97T>A		intron	N/A	NP_075556.1
	SIGLEC1	NM_001367089.1		c.4894+97T>A		intron	N/A	NP_001354018.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIGLEC1	ENST00000344754.6	TSL:1 MANE Select	c.4894+97T>A		intron	N/A	ENSP00000341141.4
	SIGLEC1	ENST00000419548.4	TSL:2	c.*41T>A		3_prime_UTR	Exon 5 of 5	ENSP00000395778.1
	SIGLEC1	ENST00000707083.1		c.4894+97T>A		intron	N/A	ENSP00000516734.1

Frequencies

GnomAD3 genomes AF: 0.0433 AC: 6592 AN: 152208 Hom.: 208 Cov.: 33

Gnomad AFR AF: 0.0103

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.0418

Gnomad ASJ AF: 0.0337

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.00889

Gnomad FIN AF: 0.0716

Gnomad MID AF: 0.0223

Gnomad NFE AF: 0.0656

Gnomad OTH AF: 0.0421

GnomAD2 exomes AF: 0.0422 AC: 5909 AN: 140104 AF XY: 0.0414

Gnomad AFR exome AF: 0.00764

Gnomad AMR exome AF: 0.0327

Gnomad ASJ exome AF: 0.0366

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0766

Gnomad NFE exome AF: 0.0641

Gnomad OTH exome AF: 0.0483

GnomAD4 exome AF: 0.0562 AC: 59788 AN: 1063220 Hom.: 1955 Cov.: 14 AF XY: 0.0549 AC XY: 29332 AN XY: 534228

African (AFR) AF: 0.00882 AC: 220 AN: 24932

American (AMR) AF: 0.0332 AC: 1116 AN: 33618

Ashkenazi Jewish (ASJ) AF: 0.0373 AC: 802 AN: 21516

East Asian (EAS) AF: 0.000147 AC: 5 AN: 34066

South Asian (SAS) AF: 0.00771 AC: 533 AN: 69132

European-Finnish (FIN) AF: 0.0771 AC: 3660 AN: 47442

Middle Eastern (MID) AF: 0.0175 AC: 86 AN: 4920

European-Non Finnish (NFE) AF: 0.0654 AC: 51077 AN: 780968

Other (OTH) AF: 0.0491 AC: 2289 AN: 46626

GnomAD4 genome AF: 0.0433 AC: 6592 AN: 152326 Hom.: 208 Cov.: 33 AF XY: 0.0423 AC XY: 3152 AN XY: 74484

African (AFR) AF: 0.0103 AC: 429 AN: 41578

American (AMR) AF: 0.0417 AC: 639 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0337 AC: 117 AN: 3472

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5188

South Asian (SAS) AF: 0.00911 AC: 44 AN: 4832

European-Finnish (FIN) AF: 0.0716 AC: 760 AN: 10614

Middle Eastern (MID) AF: 0.0205 AC: 6 AN: 292

European-Non Finnish (NFE) AF: 0.0656 AC: 4460 AN: 68016

Other (OTH) AF: 0.0416 AC: 88 AN: 2114

Alfa AF: 0.0487 Hom.: 46

Bravo AF: 0.0396

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.59
DANN	Benign	0.40
PhyloP100		-0.49
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17701662; hg19: chr20-3670512;