rs35207844

Variant names:

• chr1-160612502-G-A
• rs35207844
• NM_003037.5:c.943C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-160612502-G-A
• chr1-160612502-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_003037.5(SLAMF1):​c.943C>T​(p.Pro315Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00252 in 1,609,868 control chromosomes in the GnomAD database, including 107 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (45 hom., cov: 31)
  • Exomes 𝑓: 0.0014 (62 hom.)
• Consequence: SLAMF1 NM_003037.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.60

Genes affected

SLAMF1 (HGNC:10903): (signaling lymphocytic activation molecule family member 1) Enables SH2 domain binding activity and identical protein binding activity. Involved in several processes, including negative regulation of CD40 signaling pathway; negative regulation of cytokine production; and positive regulation of MAPK cascade. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0027861297).
• BP6: Variant 1-160612502-G-A is Benign according to our data. Variant chr1-160612502-G-A is described in ClinVar as [Benign]. Clinvar id is 717815.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 = 0.0132 (2002/152100) while in subpopulation AFR AF = 0.0454 (1883/41474). AF 95% confidence interval is 0.0437. There are 45 homozygotes in GnomAd4. There are 982 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 45 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLAMF1	NM_003037.5	c.943C>T	p.Pro315Ser	missense_variant	Exon 6 of 7	ENST00000302035.11	NP_003028.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLAMF1	ENST00000302035.11	c.943C>T	p.Pro315Ser	missense_variant	Exon 6 of 7	1	NM_003037.5	ENSP00000306190.6
SLAMF1	ENST00000538290.2	c.1026C>T	p.Ser342Ser	synonymous_variant	Exon 7 of 8	1		ENSP00000438406.2

Frequencies

GnomAD3 genomes AF: 0.0132 AC: 2001 AN: 151982 Hom.: 46 Cov.: 31

Gnomad AFR AF: 0.0455

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00576

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00910

GnomAD2 exomes AF: 0.00329 AC: 820 AN: 249572 AF XY: 0.00230

Gnomad AFR exome AF: 0.0456

Gnomad AMR exome AF: 0.00189

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000532

Gnomad OTH exome AF: 0.00148

GnomAD4 exome AF: 0.00141 AC: 2060 AN: 1457768 Hom.: 62 Cov.: 29 AF XY: 0.00121 AC XY: 879 AN XY: 725334

African (AFR) AF: 0.0501 AC: 1670 AN: 33362

American (AMR) AF: 0.00220 AC: 98 AN: 44628

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26078

East Asian (EAS) AF: 0.00 AC: 0 AN: 39624

South Asian (SAS) AF: 0.000209 AC: 18 AN: 85930

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53354

Middle Eastern (MID) AF: 0.00295 AC: 17 AN: 5754

European-Non Finnish (NFE) AF: 0.0000649 AC: 72 AN: 1108784

Other (OTH) AF: 0.00307 AC: 185 AN: 60254

GnomAD4 genome AF: 0.0132 AC: 2002 AN: 152100 Hom.: 45 Cov.: 31 AF XY: 0.0132 AC XY: 982 AN XY: 74368

African (AFR) AF: 0.0454 AC: 1883 AN: 41474

American (AMR) AF: 0.00576 AC: 88 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00125 AC: 6 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000736 AC: 5 AN: 67980

Other (OTH) AF: 0.00900 AC: 19 AN: 2110

Alfa AF: 0.00344 Hom.: 57

Bravo AF: 0.0149

ESP6500AA AF: 0.0440 AC: 194

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00398 AC: 483

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000119

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

- -

Nov 20, 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	0.098
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.0056
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.81	T
MetaRNN	Benign	0.0028	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		1.6
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.14
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.96	D
Vest4		0.16
MVP		0.80
MPC		0.75
ClinPred		0.065	T
GERP RS		3.4
Varity_R		0.12
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
Splicevardb		1.0
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

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Other links and lift over

dbSNP: rs35207844; hg19: chr1-160582292;