20-18567412-A-G

Variant names:

• chr20-18567412-A-G
• rs12624935
• ENST00000435844.3:c.-67A>G

Variant summary

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

The ENST00000435844.3(SMIM26):​c.-67A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 700,144 control chromosomes in the GnomAD database, including 5,674 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 0.13 (1303 hom., cov: 33)
  • Exomes 𝑓: 0.12 (4371 hom.)
• Consequence: SMIM26 ENST00000435844.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• Publications: 5 publications found

Genes affected

SMIM26 (HGNC:43430): (small integral membrane protein 26) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000284776 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000435844.3. 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
	SMIM26	NM_001348957.2	MANE Select	c.-67A>G		upstream_gene	N/A	NP_001335886.1	A0A096LP01-1
	SMIM26	NM_001348958.2		c.-67A>G		upstream_gene	N/A	NP_001335887.1	A0A096LP01-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMIM26	ENST00000435844.3	TSL:1	c.-67A>G		5_prime_UTR	Exon 1 of 2	ENSP00000485491.1	A0A096LP01-2
	SMIM26	ENST00000411646.2	TSL:1 MANE Select	c.-67A>G		upstream_gene	N/A	ENSP00000485316.2	A0A096LP01-1
	ENSG00000284776	ENST00000618693.4	TSL:5	c.-67A>G		upstream_gene	N/A	ENSP00000482916.1	A0A087WZV9

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19063 AN: 152100 Hom.: 1304 Cov.: 33

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.0414

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.144

GnomAD4 exome AF: 0.120 AC: 65547 AN: 547926 Hom.: 4371 Cov.: 0 AF XY: 0.114 AC XY: 33785 AN XY: 296378

African (AFR) AF: 0.115 AC: 1807 AN: 15764

American (AMR) AF: 0.203 AC: 7023 AN: 34624

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 3002 AN: 19952

East Asian (EAS) AF: 0.146 AC: 4677 AN: 32058

South Asian (SAS) AF: 0.0463 AC: 2897 AN: 62560

European-Finnish (FIN) AF: 0.127 AC: 4257 AN: 33500

Middle Eastern (MID) AF: 0.141 AC: 537 AN: 3820

European-Non Finnish (NFE) AF: 0.119 AC: 37660 AN: 315178

Other (OTH) AF: 0.121 AC: 3687 AN: 30470

GnomAD4 genome AF: 0.125 AC: 19065 AN: 152218 Hom.: 1303 Cov.: 33 AF XY: 0.126 AC XY: 9377 AN XY: 74436

African (AFR) AF: 0.115 AC: 4765 AN: 41530

American (AMR) AF: 0.183 AC: 2801 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 574 AN: 3470

East Asian (EAS) AF: 0.160 AC: 830 AN: 5178

South Asian (SAS) AF: 0.0414 AC: 200 AN: 4828

European-Finnish (FIN) AF: 0.131 AC: 1385 AN: 10602

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.118 AC: 8014 AN: 68002

Other (OTH) AF: 0.143 AC: 302 AN: 2112

Alfa AF: 0.0880 Hom.: 165

Bravo AF: 0.133

Asia WGS AF: 0.0990 AC: 343 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.40
DANN	Benign	0.39
PhyloP100		-1.4
PromoterAI		-0.084	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs12624935; hg19: chr20-18548056;