rs1378945

Positions:

• chr4-25771575-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015187.5(SEL1L3):​c.2670-3745T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 152,018 control chromosomes in the GnomAD database, including 6,826 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 0.29 (6826 hom., cov: 32)
• Consequence: SEL1L3 NM_015187.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.265

Genes affected

SEL1L3 (HGNC:29108): (SEL1L family member 3) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEL1L3	NM_015187.5	c.2670-3745T>G		intron_variant		ENST00000399878.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEL1L3	ENST00000399878.8	c.2670-3745T>G		intron_variant		1	NM_015187.5	P1
	ENST00000510905.1	n.237+1073A>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44599 AN: 151900 Hom.: 6821 Cov.: 32

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.283

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.294 AC: 44630 AN: 152018 Hom.: 6826 Cov.: 32 AF XY: 0.293 AC XY: 21741 AN XY: 74284

Gnomad4 AFR AF: 0.355

Gnomad4 AMR AF: 0.216

Gnomad4 ASJ AF: 0.247

Gnomad4 EAS AF: 0.173

Gnomad4 SAS AF: 0.346

Gnomad4 FIN AF: 0.298

Gnomad4 NFE AF: 0.282

Gnomad4 OTH AF: 0.284

Alfa AF: 0.289 Hom.: 1086

Bravo AF: 0.287

Asia WGS AF: 0.266 AC: 926 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.6
DANN	Benign	0.81

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: rs1378945; hg19: chr4-25773197;