chr1-160612423-C-T

Variant names:

• chr1-160612423-C-T
• rs2025515
• NM_003037.5:c.957+65G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003037.5(SLAMF1):​c.957+65G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000495 in 1,010,520 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000020 (0 hom., cov: 28)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: SLAMF1 NM_003037.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35
• Publications: 3 publications found

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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003037.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLAMF1	NM_003037.5	MANE Select	c.957+65G>A		intron	N/A	NP_003028.1	Q13291-1
	SLAMF1	NM_001330754.2		c.1040+65G>A		intron	N/A	NP_001317683.1	Q13291-4
	SLAMF1	NR_104399.3		n.982+65G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLAMF1	ENST00000302035.11	TSL:1 MANE Select	c.957+65G>A		intron	N/A	ENSP00000306190.6	Q13291-1
	SLAMF1	ENST00000538290.2	TSL:1	c.1040+65G>A		intron	N/A	ENSP00000438406.2	Q13291-4
	SLAMF1	ENST00000878659.1		c.867+65G>A		intron	N/A	ENSP00000548717.1

Frequencies

GnomAD3 genomes AF: 0.0000199 AC: 3 AN: 150792 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.0000730

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000233 AC: 2 AN: 859728 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 438654

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000510 AC: 1 AN: 19620

American (AMR) AF: 0.00 AC: 0 AN: 24058

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18702

East Asian (EAS) AF: 0.00 AC: 0 AN: 32154

South Asian (SAS) AF: 0.00 AC: 0 AN: 60242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44928

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4314

European-Non Finnish (NFE) AF: 0.00000162 AC: 1 AN: 616834

Other (OTH) AF: 0.00 AC: 0 AN: 38876

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0448430), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000199 AC: 3 AN: 150792 Hom.: 0 Cov.: 28 AF XY: 0.0000272 AC XY: 2 AN XY: 73518

African (AFR) AF: 0.0000730 AC: 3 AN: 41086

American (AMR) AF: 0.00 AC: 0 AN: 15166

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5108

South Asian (SAS) AF: 0.00 AC: 0 AN: 4782

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10224

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67662

Other (OTH) AF: 0.00 AC: 0 AN: 2074

Alfa AF: 0.00 Hom.: 3142

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.16
DANN	Benign	0.36
PhyloP100		-1.3

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: rs2025515; hg19: chr1-160582213;