4-25771828-C-T

Variant names:

• chr4-25771828-C-T
• rs1378946
• NM_015187.5:c.2670-3998G>A

Variant summary

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

The NM_015187.5(SEL1L3):​c.2670-3998G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 152,092 control chromosomes in the GnomAD database, including 6,226 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 0.28 (6226 hom., cov: 32)
• Consequence: SEL1L3 NM_015187.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33
• Publications: 4 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=-0.68).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.345 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEL1L3	NM_015187.5	MANE Select	c.2670-3998G>A		intron	N/A	NP_056002.2
	SEL1L3	NM_001297592.2		c.2565-3998G>A		intron	N/A	NP_001284521.1
	SEL1L3	NM_001297594.2		c.2211-3998G>A		intron	N/A	NP_001284523.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEL1L3	ENST00000399878.8	TSL:1 MANE Select	c.2670-3998G>A		intron	N/A	ENSP00000382767.3
	SEL1L3	ENST00000264868.9	TSL:1	c.2565-3998G>A		intron	N/A	ENSP00000264868.5
	SEL1L3	ENST00000502949.5	TSL:2	c.2211-3998G>A		intron	N/A	ENSP00000425438.1

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42396 AN: 151974 Hom.: 6221 Cov.: 32

Gnomad AFR AF: 0.350

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.279 AC: 42428 AN: 152092 Hom.: 6226 Cov.: 32 AF XY: 0.279 AC XY: 20742 AN XY: 74342

African (AFR) AF: 0.350 AC: 14502 AN: 41446

American (AMR) AF: 0.205 AC: 3129 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 851 AN: 3470

East Asian (EAS) AF: 0.174 AC: 899 AN: 5174

South Asian (SAS) AF: 0.339 AC: 1633 AN: 4816

European-Finnish (FIN) AF: 0.294 AC: 3102 AN: 10560

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.257 AC: 17494 AN: 68020

Other (OTH) AF: 0.270 AC: 569 AN: 2110

Alfa AF: 0.267 Hom.: 1438

Bravo AF: 0.272

Asia WGS AF: 0.263 AC: 915 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	16
DANN	Benign	0.67
PhyloP100		1.3
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: rs1378946; hg19: chr4-25773450;