1-159830096-G-A

Variant names:

• chr1-159830096-G-A
• rs148009811
• NM_020125.3:c.271G>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_020125.3(SLAMF8):​c.271G>A​(p.Gly91Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000159 in 1,614,158 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00051 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00012 (1 hom.)
• Consequence: SLAMF8 NM_020125.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.165

Genes affected

SLAMF8 (HGNC:21391): (SLAM family member 8) This gene encodes a member of the CD2 family of cell surface proteins involved in lymphocyte activation. These proteins are characterized by Ig domains. This protein is expressed in lymphoid tissues, and studies of a similar protein in mouse suggest that it may function during B cell lineage commitment. The gene is found in a region of chromosome 1 containing many CD2 genes. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.010974675).
• BP6: Variant 1-159830096-G-A is Benign according to our data. Variant chr1-159830096-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2397357.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLAMF8	NM_020125.3	c.271G>A	p.Gly91Arg	missense_variant	Exon 2 of 5	ENST00000289707.10	NP_064510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLAMF8	ENST00000289707.10	c.271G>A	p.Gly91Arg	missense_variant	Exon 2 of 5	1	NM_020125.3	ENSP00000289707.5
SLAMF8	ENST00000368104.4	c.41-2780G>A		intron_variant	Intron 1 of 3	2		ENSP00000357084.4
SLAMF8	ENST00000471286.5	n.89G>A		non_coding_transcript_exon_variant	Exon 1 of 4	3

Frequencies

GnomAD3 genomes AF: 0.000506 AC: 77 AN: 152180 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00159

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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: 0.000132

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000191 AC: 48 AN: 251296 Hom.: 0 AF XY: 0.000199 AC XY: 27 AN XY: 135846

Gnomad AFR exome AF: 0.00154

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000163

Gnomad SAS exome AF: 0.000392

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000123 AC: 180 AN: 1461860 Hom.: 1 Cov.: 33 AF XY: 0.000121 AC XY: 88 AN XY: 727234

Gnomad4 AFR exome AF: 0.00128

Gnomad4 AMR exome AF: 0.0000671

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000176

Gnomad4 SAS exome AF: 0.000417

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000665

Gnomad4 OTH exome AF: 0.000232

GnomAD4 genome AF: 0.000506 AC: 77 AN: 152298 Hom.: 0 Cov.: 33 AF XY: 0.000456 AC XY: 34 AN XY: 74480

Gnomad4 AFR AF: 0.00159

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000164 Hom.: 0

Bravo AF: 0.000461

ESP6500AA AF: 0.00159 AC: 7

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000148 AC: 18

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jan 26, 2022

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	12
DANN	Benign	0.86
DEOGEN2	Benign	0.0031	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.011	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.97	L
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.040	N
REVEL	Benign	0.018
Sift	Benign	0.35	T
Sift4G	Benign	0.85	T
Polyphen		0.013	B
Vest4		0.13
MutPred		0.36		Loss of catalytic residue at G91 (P = 0.115);
MVP		0.081
MPC		0.067
ClinPred		0.0018	T
GERP RS		1.5
Varity_R		0.032
gMVP		0.40

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

Publications

LitVar

Other links and lift over

dbSNP: rs148009811; hg19: chr1-159799886;