rs2271622

Variant names:

• chr2-11160606-C-T
• rs2271622
• NM_152391.5:c.227-19C>T

Variant summary

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

The NM_152391.5(SLC66A3):​c.227-19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 1,613,580 control chromosomes in the GnomAD database, including 183,717 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 0.40 (13352 hom., cov: 31)
  • Exomes 𝑓: 0.48 (170365 hom.)
• Consequence: SLC66A3 NM_152391.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.36
• Publications: 16 publications found

Genes affected

SLC66A3 (HGNC:28503): (solute carrier family 66 member 3) 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 (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC66A3	NM_152391.5	c.227-19C>T		intron_variant	Intron 2 of 6	ENST00000295083.8	NP_689604.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC66A3	ENST00000295083.8	c.227-19C>T		intron_variant	Intron 2 of 6	1	NM_152391.5	ENSP00000295083.3

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60270 AN: 151814 Hom.: 13347 Cov.: 31

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.495

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.412

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.513

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.417

GnomAD2 exomes AF: 0.454 AC: 114063 AN: 251476 AF XY: 0.462

Gnomad AFR exome AF: 0.182

Gnomad AMR exome AF: 0.426

Gnomad ASJ exome AF: 0.425

Gnomad EAS exome AF: 0.480

Gnomad FIN exome AF: 0.424

Gnomad NFE exome AF: 0.491

Gnomad OTH exome AF: 0.479

GnomAD4 exome AF: 0.479 AC: 700033 AN: 1461650 Hom.: 170365 Cov.: 55 AF XY: 0.480 AC XY: 349276 AN XY: 727144

African (AFR) AF: 0.183 AC: 6133 AN: 33480

American (AMR) AF: 0.427 AC: 19097 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.420 AC: 10983 AN: 26132

East Asian (EAS) AF: 0.467 AC: 18535 AN: 39700

South Asian (SAS) AF: 0.498 AC: 42935 AN: 86254

European-Finnish (FIN) AF: 0.427 AC: 22820 AN: 53416

Middle Eastern (MID) AF: 0.495 AC: 2855 AN: 5768

European-Non Finnish (NFE) AF: 0.493 AC: 548544 AN: 1111798

Other (OTH) AF: 0.466 AC: 28131 AN: 60380

GnomAD4 genome AF: 0.397 AC: 60284 AN: 151930 Hom.: 13352 Cov.: 31 AF XY: 0.396 AC XY: 29410 AN XY: 74248

African (AFR) AF: 0.193 AC: 8007 AN: 41462

American (AMR) AF: 0.445 AC: 6792 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.412 AC: 1429 AN: 3470

East Asian (EAS) AF: 0.463 AC: 2382 AN: 5146

South Asian (SAS) AF: 0.513 AC: 2465 AN: 4806

European-Finnish (FIN) AF: 0.414 AC: 4376 AN: 10562

Middle Eastern (MID) AF: 0.493 AC: 144 AN: 292

European-Non Finnish (NFE) AF: 0.491 AC: 33365 AN: 67936

Other (OTH) AF: 0.417 AC: 874 AN: 2094

Alfa AF: 0.463 Hom.: 64716

Bravo AF: 0.385

Asia WGS AF: 0.448 AC: 1561 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.13
DANN	Benign	0.46
PhyloP100		-2.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2271622; hg19: chr2-11300732; COSMIC: COSV54466390;