4-25808474-G-A

Variant names:

• chr4-25808474-G-A
• rs959903
• NM_015187.5:c.1565-3722C>T

Variant summary

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

The NM_015187.5(SEL1L3):​c.1565-3722C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 152,040 control chromosomes in the GnomAD database, including 5,239 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 0.25 (5239 hom., cov: 32)
• Consequence: SEL1L3 NM_015187.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.635
• Publications: 7 publications found

Genes affected

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.318 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.1565-3722C>T		intron	N/A	NP_056002.2
	SEL1L3	NM_001297592.2		c.1460-3722C>T		intron	N/A	NP_001284521.1
	SEL1L3	NM_001297594.2		c.1106-3722C>T		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.1565-3722C>T		intron	N/A	ENSP00000382767.3
	SEL1L3	ENST00000264868.9	TSL:1	c.1460-3722C>T		intron	N/A	ENSP00000264868.5
	SEL1L3	ENST00000502949.5	TSL:2	c.1106-3722C>T		intron	N/A	ENSP00000425438.1

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38689 AN: 151922 Hom.: 5230 Cov.: 32

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.369

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.257

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

GnomAD4 genome AF: 0.255 AC: 38725 AN: 152040 Hom.: 5239 Cov.: 32 AF XY: 0.254 AC XY: 18881 AN XY: 74296

African (AFR) AF: 0.186 AC: 7712 AN: 41468

American (AMR) AF: 0.326 AC: 4979 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1142 AN: 3468

East Asian (EAS) AF: 0.149 AC: 770 AN: 5170

South Asian (SAS) AF: 0.263 AC: 1264 AN: 4814

European-Finnish (FIN) AF: 0.257 AC: 2712 AN: 10558

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.282 AC: 19201 AN: 67974

Other (OTH) AF: 0.260 AC: 548 AN: 2110

Alfa AF: 0.274 Hom.: 22412

Bravo AF: 0.254

Asia WGS AF: 0.215 AC: 749 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.047
DANN	Benign	0.79
PhyloP100		-0.64
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: rs959903; hg19: chr4-25810096;