rs1378945

Variant names:

• chr4-25771575-A-C
• rs1378945
• NM_015187.5:c.2670-3745T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

Genes affected

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

ENSG00000250541 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015187.5. 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
	SEL1L3	NM_015187.5	MANE Select	c.2670-3745T>G		intron	N/A	NP_056002.2	Q68CR1-1
	SEL1L3	NM_001297592.2		c.2565-3745T>G		intron	N/A	NP_001284521.1	Q68CR1-2
	SEL1L3	NM_001297594.2		c.2211-3745T>G		intron	N/A	NP_001284523.1	Q68CR1-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEL1L3	ENST00000399878.8	TSL:1 MANE Select	c.2670-3745T>G		intron	N/A	ENSP00000382767.3	Q68CR1-1
	SEL1L3	ENST00000264868.9	TSL:1	c.2565-3745T>G		intron	N/A	ENSP00000264868.5	Q68CR1-2
	SEL1L3	ENST00000929301.1		c.2775-3745T>G		intron	N/A	ENSP00000599360.1

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

African (AFR) AF: 0.355 AC: 14697 AN: 41430

American (AMR) AF: 0.216 AC: 3305 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 857 AN: 3470

East Asian (EAS) AF: 0.173 AC: 893 AN: 5170

South Asian (SAS) AF: 0.346 AC: 1670 AN: 4820

European-Finnish (FIN) AF: 0.298 AC: 3143 AN: 10544

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.282 AC: 19175 AN: 67982

Other (OTH) AF: 0.284 AC: 600 AN: 2112

Alfa AF: 0.284 Hom.: 9341

Bravo AF: 0.287

Asia WGS AF: 0.266 AC: 926 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.6
DANN	Benign	0.81
PhyloP100		0.27
Mutation Taster		=100/0	polymorphism (auto)

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: rs1378945; hg19: chr4-25773197;