1-169704733-C-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_000655.5(SELL):c.601G>C(p.Glu201Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00066 in 1,546,422 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.0032 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00039 (4 hom.)
• Consequence: SELL NM_000655.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.874

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 1-169704733-C-G is Benign according to our data. Variant chr1-169704733-C-G is described in ClinVar as [Benign]. Clinvar id is 723964.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SELL	NM_000655.5	c.601G>C	p.Glu201Gln	missense_variant	5/9	ENST00000236147.6
SELL	NR_029467.2	n.570G>C		non_coding_transcript_exon_variant	3/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SELL	ENST00000236147.6	c.601G>C	p.Glu201Gln	missense_variant	5/9	1	NM_000655.5	P1

Frequencies

GnomAD3 genomes AF: 0.00317 AC: 483 AN: 152126 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0113

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000590

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.000853 AC: 133 AN: 156006 Hom.: 2 AF XY: 0.000608 AC XY: 50 AN XY: 82302

Gnomad AFR exome AF: 0.0140

Gnomad AMR exome AF: 0.000530

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000440

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000830

Gnomad OTH exome AF: 0.000460

GnomAD4 exome AF: 0.000387 AC: 539 AN: 1394178 Hom.: 4 Cov.: 31 AF XY: 0.000323 AC XY: 222 AN XY: 687162

Gnomad4 AFR exome AF: 0.0138

Gnomad4 AMR exome AF: 0.000478

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000380

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000437

Gnomad4 OTH exome AF: 0.000606

GnomAD4 genome AF: 0.00317 AC: 482 AN: 152244 Hom.: 4 Cov.: 32 AF XY: 0.00293 AC XY: 218 AN XY: 74426

Gnomad4 AFR AF: 0.0112

Gnomad4 AMR AF: 0.000589

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.000454 Hom.: 0

Bravo AF: 0.00349

ESP6500AA AF: 0.00864 AC: 30

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000484 AC: 31

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

Apr 24, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.73
Cadd	Benign	18
Dann	Benign	0.85
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.060	N
LIST_S2	Benign	0.13	T
MetaRNN	Benign	0.0030	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.010
Sift	Benign	0.18	T
Sift4G	Benign	0.31	T
Vest4		0.060
MVP		0.35
MPC		0.021
ClinPred		0.0014	T
GERP RS		-1.4

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.30		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.30		Position offset: -3

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

Publications

LitVar

Other links and lift over

dbSNP: rs2229568; hg19: chr1-169673874;