rs17631940

Variant names:

• chr17-35491111-G-A
• rs17631940
• NM_001363830.2:c.87-10916C>T

Variant summary

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

The NM_001363830.2(SLFN12L):​c.87-10916C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 773,562 control chromosomes in the GnomAD database, including 85,683 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 0.49 (18628 hom., cov: 32)
  • Exomes 𝑓: 0.45 (67055 hom.)
• Consequence: SLFN12L NM_001363830.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.53
• Publications: 8 publications found

Genes affected

SLFN12L (HGNC:33920): (schlafen family member 12 like) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

E2F3P1 (HGNC:3116): (E2F transcription factor 3 pseudogene 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLFN12L	NM_001363830.2	c.87-10916C>T		intron_variant	Intron 2 of 4	ENST00000628453.4	NP_001350759.2
E2F3P1		n.35491111G>A		intragenic_variant
SLFN12L	NM_001195790.3	c.-287-3139C>T		intron_variant	Intron 2 of 5		NP_001182719.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLFN12L	ENST00000628453.4	c.87-10916C>T		intron_variant	Intron 2 of 4	5	NM_001363830.2	ENSP00000487397.4
E2F3P1	ENST00000589887.1	n.1103G>A		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes AF: 0.490 AC: 74467 AN: 151898 Hom.: 18625 Cov.: 32

Gnomad AFR AF: 0.556

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.524

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.502

GnomAD4 exome AF: 0.454 AC: 282369 AN: 621548 Hom.: 67055 Cov.: 6 AF XY: 0.449 AC XY: 151683 AN XY: 337526

African (AFR) AF: 0.559 AC: 9691 AN: 17332

American (AMR) AF: 0.419 AC: 17390 AN: 41472

Ashkenazi Jewish (ASJ) AF: 0.520 AC: 10294 AN: 19794

East Asian (EAS) AF: 0.292 AC: 10438 AN: 35780

South Asian (SAS) AF: 0.304 AC: 20570 AN: 67738

European-Finnish (FIN) AF: 0.404 AC: 20657 AN: 51192

Middle Eastern (MID) AF: 0.470 AC: 1902 AN: 4050

European-Non Finnish (NFE) AF: 0.501 AC: 176151 AN: 351742

Other (OTH) AF: 0.471 AC: 15276 AN: 32448

GnomAD4 genome AF: 0.490 AC: 74500 AN: 152014 Hom.: 18628 Cov.: 32 AF XY: 0.479 AC XY: 35556 AN XY: 74304

African (AFR) AF: 0.555 AC: 23011 AN: 41440

American (AMR) AF: 0.446 AC: 6818 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.524 AC: 1815 AN: 3466

East Asian (EAS) AF: 0.284 AC: 1468 AN: 5166

South Asian (SAS) AF: 0.298 AC: 1437 AN: 4816

European-Finnish (FIN) AF: 0.398 AC: 4207 AN: 10574

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.502 AC: 34109 AN: 67950

Other (OTH) AF: 0.501 AC: 1057 AN: 2108

Alfa AF: 0.493 Hom.: 17343

Bravo AF: 0.501

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	15
DANN	Benign	0.80
PhyloP100		3.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17631940; hg19: chr17-33818130; COSMIC: COSV53470944; COSMIC: COSV53470944;