rs6819016

Variant names:

• chr4-25773412-T-C
• rs6819016
• NM_015187.5:c.2669+2865A>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.2669+2865A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,098 control chromosomes in the GnomAD database, including 1,108 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 0.12 (1108 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SEL1L3 NM_015187.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.879
• Publications: 3 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.161 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.2669+2865A>G		intron	N/A	NP_056002.2	Q68CR1-1
	SEL1L3	NM_001297592.2		c.2564+2865A>G		intron	N/A	NP_001284521.1	Q68CR1-2
	SEL1L3	NM_001297594.2		c.2210+2865A>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.2669+2865A>G		intron	N/A	ENSP00000382767.3	Q68CR1-1
	SEL1L3	ENST00000264868.9	TSL:1	c.2564+2865A>G		intron	N/A	ENSP00000264868.5	Q68CR1-2
	SEL1L3	ENST00000929301.1		c.2774+2865A>G		intron	N/A	ENSP00000599360.1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18066 AN: 151978 Hom.: 1108 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.0942

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.0954

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.120

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.119 AC: 18071 AN: 152098 Hom.: 1108 Cov.: 32 AF XY: 0.119 AC XY: 8825 AN XY: 74362

African (AFR) AF: 0.157 AC: 6517 AN: 41436

American (AMR) AF: 0.109 AC: 1671 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 355 AN: 3470

East Asian (EAS) AF: 0.0942 AC: 487 AN: 5172

South Asian (SAS) AF: 0.170 AC: 820 AN: 4818

European-Finnish (FIN) AF: 0.0954 AC: 1010 AN: 10592

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.101 AC: 6879 AN: 68008

Other (OTH) AF: 0.122 AC: 259 AN: 2116

Alfa AF: 0.110 Hom.: 1786

Bravo AF: 0.121

Asia WGS AF: 0.133 AC: 463 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.7
DANN	Benign	0.63
PhyloP100		0.88
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: rs6819016; hg19: chr4-25775034;