1-169708782-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_000655.5(SELL):c.107C>G(p.Thr36Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00436 in 1,555,872 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0050 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0043 (40 hom.)
• Consequence: SELL NM_000655.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.509

Genes affected

SELL (HGNC:10720): (selectin L) This gene encodes a cell surface adhesion molecule that belongs to a family of adhesion/homing receptors. The encoded protein contains a C-type lectin-like domain, a calcium-binding epidermal growth factor-like domain, and two short complement-like repeats. The gene product is required for binding and subsequent rolling of leucocytes on endothelial cells, facilitating their migration into secondary lymphoid organs and inflammation sites. Single-nucleotide polymorphisms in this gene have been associated with various diseases including immunoglobulin A nephropathy. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Oct 2009]

FIRRM (HGNC:25565): (FIGNL1 interacting regulator of recombination and mitosis)

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0027054846).
• BP6: Variant 1-169708782-G-C is Benign according to our data. Variant chr1-169708782-G-C is described in ClinVar as [Benign]. Clinvar id is 713751.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SELL	NM_000655.5	c.107C>G	p.Thr36Ser	missense_variant	3/9	ENST00000236147.6
SELL	NR_029467.2	n.76C>G		non_coding_transcript_exon_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SELL	ENST00000236147.6	c.107C>G	p.Thr36Ser	missense_variant	3/9	1	NM_000655.5	P1

Frequencies

GnomAD3 genomes AF: 0.00496 AC: 755 AN: 152126 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00248

Gnomad FIN AF: 0.0239

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00617

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00515 AC: 839 AN: 162810 Hom.: 5 AF XY: 0.00482 AC XY: 414 AN XY: 85806

Gnomad AFR exome AF: 0.000227

Gnomad AMR exome AF: 0.00168

Gnomad ASJ exome AF: 0.00197

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00155

Gnomad FIN exome AF: 0.0234

Gnomad NFE exome AF: 0.00513

Gnomad OTH exome AF: 0.00309

GnomAD4 exome AF: 0.00430 AC: 6033 AN: 1403628 Hom.: 40 Cov.: 33 AF XY: 0.00435 AC XY: 3015 AN XY: 692838

Gnomad4 AFR exome AF: 0.000314

Gnomad4 AMR exome AF: 0.00175

Gnomad4 ASJ exome AF: 0.00258

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00169

Gnomad4 FIN exome AF: 0.0227

Gnomad4 NFE exome AF: 0.00409

Gnomad4 OTH exome AF: 0.00349

GnomAD4 genome AF: 0.00496 AC: 755 AN: 152244 Hom.: 5 Cov.: 32 AF XY: 0.00539 AC XY: 401 AN XY: 74436

Gnomad4 AFR AF: 0.000722

Gnomad4 AMR AF: 0.00144

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00248

Gnomad4 FIN AF: 0.0239

Gnomad4 NFE AF: 0.00617

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00501 Hom.: 5

Bravo AF: 0.00290

TwinsUK AF: 0.00297 AC: 11

ALSPAC AF: 0.00285 AC: 11

ESP6500AA AF: 0.000264 AC: 1

ESP6500EA AF: 0.00450 AC: 37

ExAC AF: 0.00315 AC: 349

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 13, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.61
Cadd	Benign	13
Dann	Benign	0.90
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.48	T
MetaRNN	Benign	0.0027	T
MetaSVM	Benign	-0.92	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.060
Sift	Benign	0.37	T
Sift4G	Benign	0.65	T
Vest4		0.091
MVP		0.38
MPC		0.019
ClinPred		0.0032	T
GERP RS		1.6

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs61761863; hg19: chr1-169677923;