6-130827597-G-A

Variant names:

• chr6-130827597-G-A
• rs1044303
• NM_001195597.2:c.184G>A

Variant summary

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

The NM_001195597.2(SMLR1):​c.184G>A​(p.Val62Met) variant causes a missense change. The variant allele was found at a frequency of 0.33 in 1,535,464 control chromosomes in the GnomAD database, including 89,532 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 0.37 (11134 hom., cov: 31)
  • Exomes 𝑓: 0.33 (78398 hom.)
• Consequence: SMLR1 NM_001195597.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.53
• Publications: 26 publications found

Genes affected

SMLR1 (HGNC:44670): (small leucine rich protein 1) Predicted to be integral component of membrane. [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 (MetaRNN=6.7580086E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001195597.2. 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
	SMLR1	NM_001195597.2	MANE Select	c.184G>A	p.Val62Met	missense	Exon 1 of 2	NP_001182526.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMLR1	ENST00000541421.2	TSL:1 MANE Select	c.184G>A	p.Val62Met	missense	Exon 1 of 2	ENSP00000456026.1

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56306 AN: 151648 Hom.: 11119 Cov.: 31

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.650

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.347

GnomAD2 exomes AF: 0.397 AC: 54294 AN: 136896 AF XY: 0.394

Gnomad AFR exome AF: 0.440

Gnomad AMR exome AF: 0.516

Gnomad ASJ exome AF: 0.231

Gnomad EAS exome AF: 0.644

Gnomad FIN exome AF: 0.412

Gnomad NFE exome AF: 0.285

Gnomad OTH exome AF: 0.341

GnomAD4 exome AF: 0.326 AC: 450885 AN: 1383698 Hom.: 78398 Cov.: 42 AF XY: 0.329 AC XY: 224372 AN XY: 682798

African (AFR) AF: 0.437 AC: 13814 AN: 31584

American (AMR) AF: 0.500 AC: 17864 AN: 35698

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 5816 AN: 25176

East Asian (EAS) AF: 0.646 AC: 23070 AN: 35734

South Asian (SAS) AF: 0.478 AC: 37914 AN: 79236

European-Finnish (FIN) AF: 0.406 AC: 13765 AN: 33902

Middle Eastern (MID) AF: 0.260 AC: 1480 AN: 5694

European-Non Finnish (NFE) AF: 0.294 AC: 317229 AN: 1078776

Other (OTH) AF: 0.344 AC: 19933 AN: 57898

GnomAD4 genome AF: 0.371 AC: 56360 AN: 151766 Hom.: 11134 Cov.: 31 AF XY: 0.380 AC XY: 28185 AN XY: 74154

African (AFR) AF: 0.432 AC: 17841 AN: 41328

American (AMR) AF: 0.436 AC: 6636 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 798 AN: 3470

East Asian (EAS) AF: 0.650 AC: 3347 AN: 5148

South Asian (SAS) AF: 0.487 AC: 2340 AN: 4800

European-Finnish (FIN) AF: 0.421 AC: 4439 AN: 10540

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.292 AC: 19854 AN: 67934

Other (OTH) AF: 0.350 AC: 737 AN: 2106

Alfa AF: 0.315 Hom.: 26382

Bravo AF: 0.376

TwinsUK AF: 0.308 AC: 1142

ALSPAC AF: 0.292 AC: 1126

ExAC AF: 0.337 AC: 5946

Asia WGS AF: 0.576 AC: 1999 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.076	T
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.69	T
MetaRNN	Benign	0.0000068	T
MutationAssessor	Benign	0.81	L
PhyloP100		4.5
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-3.0	D
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.15
GERP RS		5.2
PromoterAI		-0.051	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.28
gMVP		0.12
Mutation Taster		=61/39	polymorphism

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: rs1044303; hg19: chr6-131148737; COSMIC: COSV73407205;