chr1-159953444-C-T

Variant names:

• chr1-159953444-C-T
• rs34540580
• NM_033438.4:c.256G>A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001146173.2(SLAMF9):​c.255+1G>A variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00428 in 1,614,212 control chromosomes in the GnomAD database, including 263 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (119 hom., cov: 33)
  • Exomes 𝑓: 0.0024 (144 hom.)
• Consequence: SLAMF9 NM_001146173.2 splice_donor, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.563

Genes affected

SLAMF9 (HGNC:18430): (SLAM family member 9) This gene encodes a member of the signaling lymphocytic activation molecule family. The encoded protein is a cell surface molecule that consists of two extracellular immunoglobulin domains, a transmembrane domain and a short cytoplasmic tail that lacks the signal transduction motifs found in other family members. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Apr 2009]

LOC124904438 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0032785237).
• BP6: Variant 1-159953444-C-T is Benign according to our data. Variant chr1-159953444-C-T is described in ClinVar as [Benign]. Clinvar id is 767714.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLAMF9	NM_033438.4	c.256G>A	p.Val86Met	missense_variant	Exon 2 of 4	ENST00000368093.4	NP_254273.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLAMF9	ENST00000368093.4	c.256G>A	p.Val86Met	missense_variant	Exon 2 of 4	1	NM_033438.4	ENSP00000357072.3
SLAMF9	ENST00000368092.7	c.256G>A	p.Val86Met	missense_variant	Exon 2 of 3	1		ENSP00000357071.3
SLAMF9	ENST00000466773.5	n.48+1G>A		splice_donor_variant, intron_variant	Intron 1 of 2	3
SLAMF9	ENST00000489098.1	n.302+1G>A		splice_donor_variant, intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.0224 AC: 3417 AN: 152210 Hom.: 119 Cov.: 33

Gnomad AFR AF: 0.0781

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00779

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000220

Gnomad OTH AF: 0.0153

GnomAD3 exomes AF: 0.00575 AC: 1446 AN: 251480 Hom.: 52 AF XY: 0.00402 AC XY: 546 AN XY: 135914

Gnomad AFR exome AF: 0.0787

Gnomad AMR exome AF: 0.00298

Gnomad ASJ exome AF: 0.00139

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000392

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000211

Gnomad OTH exome AF: 0.00228

GnomAD4 exome AF: 0.00237 AC: 3468 AN: 1461884 Hom.: 144 Cov.: 35 AF XY: 0.00206 AC XY: 1500 AN XY: 727242

Gnomad4 AFR exome AF: 0.0828

Gnomad4 AMR exome AF: 0.00324

Gnomad4 ASJ exome AF: 0.00149

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000510

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000845

Gnomad4 OTH exome AF: 0.00528

GnomAD4 genome AF: 0.0226 AC: 3444 AN: 152328 Hom.: 119 Cov.: 33 AF XY: 0.0220 AC XY: 1639 AN XY: 74504

Gnomad4 AFR AF: 0.0786

Gnomad4 AMR AF: 0.00778

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000221

Gnomad4 OTH AF: 0.0151

Alfa AF: 0.00491 Hom.: 24

Bravo AF: 0.0250

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0726 AC: 320

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00692 AC: 840

Asia WGS AF: 0.00779 AC: 27 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.000474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 13, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.55
CADD	Pathogenic	26
DANN	Benign	0.87
DEOGEN2	Benign	0.0093	.;T
Eigen	Benign	0.15
Eigen_PC	Benign	0.051
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.83	T;T
MetaRNN	Benign	0.0033	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M;M
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.11
Sift	Uncertain	0.0040	D;D
Sift4G	Uncertain	0.0070	D;D
Polyphen		0.87	P;D
Vest4		0.50
MVP		0.50
MPC		0.18
ClinPred		0.032	T
GERP RS		2.1
Varity_R		0.090
gMVP		0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs34540580; hg19: chr1-159923234;