rs4627080

Variant names:

• chr11-9314802-T-G
• rs4627080
• NM_015012.4:c.-361A>C

Variant summary

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

The NM_015012.4(TMEM41B):​c.-361A>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 205,604 control chromosomes in the GnomAD database, including 2,333 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 0.14 (2007 hom., cov: 35)
  • Exomes 𝑓: 0.099 (326 hom.)
• Consequence: TMEM41B NM_015012.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0170
• Publications: 11 publications found

Genes affected

TMEM41B (HGNC:28948): (transmembrane protein 41B) Involved in autophagosome assembly. Located in endoplasmic reticulum membrane and mitochondria-associated endoplasmic reticulum 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=-0.69).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015012.4. 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
	TMEM41B	NM_015012.4	MANE Select	c.-361A>C		upstream_gene	N/A	NP_055827.1	Q5BJD5-1
	TMEM41B	NM_001165030.3		c.-361A>C		upstream_gene	N/A	NP_001158502.1	Q5BJD5-3
	TMEM41B	NR_028491.3		n.-209A>C		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM41B	ENST00000528080.6	TSL:1 MANE Select	c.-361A>C		upstream_gene	N/A	ENSP00000433126.1	Q5BJD5-1
	TMEM41B	ENST00000611268.4	TSL:1	c.-361A>C		upstream_gene	N/A	ENSP00000480141.1	Q5BJD5-1
	TMEM41B	ENST00000299596.8	TSL:1	n.-361A>C		upstream_gene	N/A	ENSP00000299596.4	Q5BJD5-1

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21100 AN: 152146 Hom.: 2005 Cov.: 35

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.0849

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0757

Gnomad OTH AF: 0.139

GnomAD4 exome AF: 0.0990 AC: 5283 AN: 53340 Hom.: 326 Cov.: 0 AF XY: 0.102 AC XY: 2816 AN XY: 27492

African (AFR) AF: 0.247 AC: 408 AN: 1650

American (AMR) AF: 0.161 AC: 196 AN: 1220

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 263 AN: 2108

East Asian (EAS) AF: 0.119 AC: 420 AN: 3534

South Asian (SAS) AF: 0.186 AC: 751 AN: 4028

European-Finnish (FIN) AF: 0.0748 AC: 241 AN: 3224

Middle Eastern (MID) AF: 0.122 AC: 38 AN: 312

European-Non Finnish (NFE) AF: 0.0753 AC: 2544 AN: 33778

Other (OTH) AF: 0.121 AC: 422 AN: 3486

GnomAD4 genome AF: 0.139 AC: 21131 AN: 152264 Hom.: 2007 Cov.: 35 AF XY: 0.140 AC XY: 10391 AN XY: 74448

African (AFR) AF: 0.255 AC: 10582 AN: 41550

American (AMR) AF: 0.145 AC: 2214 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 406 AN: 3468

East Asian (EAS) AF: 0.107 AC: 554 AN: 5184

South Asian (SAS) AF: 0.199 AC: 960 AN: 4820

European-Finnish (FIN) AF: 0.0849 AC: 901 AN: 10618

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0757 AC: 5149 AN: 68006

Other (OTH) AF: 0.139 AC: 294 AN: 2114

Alfa AF: 0.113 Hom.: 213

Bravo AF: 0.148

Asia WGS AF: 0.161 AC: 558 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	7.2
DANN	Benign	0.39
PhyloP100		-0.017
PromoterAI		-0.12	Neutral

Splicing

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

Other links and lift over

dbSNP: rs4627080; hg19: chr11-9336349;