4-25759784-A-G

Variant names:

• chr4-25759784-A-G
• rs11731086
• NM_015187.5:c.2956-716T>C

Variant summary

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

The NM_015187.5(SEL1L3):​c.2956-716T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 152,138 control chromosomes in the GnomAD database, including 11,511 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 0.39 (11504 hom., cov: 31)
  • Exomes 𝑓: 0.39 (7 hom.)
• Consequence: SEL1L3 NM_015187.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.51
• Publications: 4 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.455 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.2956-716T>C		intron	N/A	NP_056002.2
	SEL1L3	NM_001297592.2		c.2851-716T>C		intron	N/A	NP_001284521.1
	SEL1L3	NM_001297594.2		c.2497-716T>C		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.2956-716T>C		intron	N/A	ENSP00000382767.3
	SEL1L3	ENST00000264868.9	TSL:1	c.2851-716T>C		intron	N/A	ENSP00000264868.5
	SEL1L3	ENST00000513416.5	TSL:2	n.194T>C		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58601 AN: 151924 Hom.: 11478 Cov.: 31

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.369

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.409

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.397

GnomAD4 exome AF: 0.385 AC: 37 AN: 96 Hom.: 7 Cov.: 0 AF XY: 0.338 AC XY: 23 AN XY: 68

African (AFR) AF: 0.250 AC: 1 AN: 4

American (AMR) AF: 0.750 AC: 3 AN: 4

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2 AN: 2

East Asian (EAS) AF: 0.750 AC: 3 AN: 4

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.750 AC: 3 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.321 AC: 25 AN: 78

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.386 AC: 58677 AN: 152042 Hom.: 11504 Cov.: 31 AF XY: 0.393 AC XY: 29195 AN XY: 74320

African (AFR) AF: 0.379 AC: 15696 AN: 41444

American (AMR) AF: 0.464 AC: 7081 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 1437 AN: 3470

East Asian (EAS) AF: 0.371 AC: 1915 AN: 5164

South Asian (SAS) AF: 0.442 AC: 2132 AN: 4822

European-Finnish (FIN) AF: 0.409 AC: 4320 AN: 10572

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.365 AC: 24779 AN: 67980

Other (OTH) AF: 0.400 AC: 845 AN: 2114

Alfa AF: 0.376 Hom.: 18523

Bravo AF: 0.391

Asia WGS AF: 0.399 AC: 1390 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.17
DANN	Benign	0.34
PhyloP100		-1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.97
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: rs11731086; hg19: chr4-25761406;