rs7718767

Variant names:

• chr5-171791134-G-A
• rs7718767
• NM_001289970.2:c.*46G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-171791134-G-A
• chr5-171791134-G-T

Variant summary

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

The NM_001289970.2(SMIM23):​c.*46G>A variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 1,437,876 control chromosomes in the GnomAD database, including 118,920 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.36 (10328 hom., cov: 33)
  • Exomes 𝑓: 0.41 (108592 hom.)
• Consequence: SMIM23 NM_001289970.2 splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.289
• Publications: 4 publications found

Genes affected

SMIM23 (HGNC:34440): (small integral membrane protein 23) Predicted to be located in plasma membrane. 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=-0.7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001289970.2. 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
	SMIM23	NM_001289970.2	MANE Select	c.*46G>A		splice_region	Exon 4 of 4	NP_001276899.1	A6NLE4
	SMIM23	NM_001289970.2	MANE Select	c.*46G>A		3_prime_UTR	Exon 4 of 4	NP_001276899.1	A6NLE4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMIM23	ENST00000523047.4	TSL:2 MANE Select	c.*46G>A		splice_region	Exon 4 of 4	ENSP00000430818.4	A6NLE4
	SMIM23	ENST00000523047.4	TSL:2 MANE Select	c.*46G>A		3_prime_UTR	Exon 4 of 4	ENSP00000430818.4	A6NLE4
	SMIM23	ENST00000639838.1	TSL:5	n.*46G>A		non_coding_transcript_exon	Exon 4 of 8	ENSP00000490990.1	A6NLE4

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54318 AN: 151968 Hom.: 10321 Cov.: 33

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.500

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.359

GnomAD4 exome AF: 0.406 AC: 522648 AN: 1285790 Hom.: 108592 Cov.: 26 AF XY: 0.402 AC XY: 251492 AN XY: 624846

African (AFR) AF: 0.221 AC: 6280 AN: 28366

American (AMR) AF: 0.338 AC: 7209 AN: 21326

Ashkenazi Jewish (ASJ) AF: 0.451 AC: 8650 AN: 19162

East Asian (EAS) AF: 0.470 AC: 16416 AN: 34956

South Asian (SAS) AF: 0.221 AC: 14003 AN: 63364

European-Finnish (FIN) AF: 0.484 AC: 14539 AN: 30010

Middle Eastern (MID) AF: 0.324 AC: 1168 AN: 3608

European-Non Finnish (NFE) AF: 0.420 AC: 433240 AN: 1031390

Other (OTH) AF: 0.394 AC: 21143 AN: 53608

GnomAD4 genome AF: 0.357 AC: 54351 AN: 152086 Hom.: 10328 Cov.: 33 AF XY: 0.362 AC XY: 26906 AN XY: 74340

African (AFR) AF: 0.226 AC: 9383 AN: 41514

American (AMR) AF: 0.362 AC: 5534 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 1560 AN: 3470

East Asian (EAS) AF: 0.500 AC: 2581 AN: 5164

South Asian (SAS) AF: 0.231 AC: 1113 AN: 4826

European-Finnish (FIN) AF: 0.496 AC: 5241 AN: 10576

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.409 AC: 27797 AN: 67944

Other (OTH) AF: 0.359 AC: 756 AN: 2108

Alfa AF: 0.365 Hom.: 5691

Bravo AF: 0.349

Asia WGS AF: 0.346 AC: 1204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	3.1
DANN	Benign	0.91
PhyloP100		-0.29

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: rs7718767; hg19: chr5-171218138;