rs2271247

Variant names:

• chr9-105694607-A-C
• rs2271247
• NM_018112.3:c.-54A>C

Your query was ambiguous. Multiple possible variants found:

• chr9-105694607-A-C
• chr9-105694607-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_018112.3(TMEM38B):​c.-54A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 1,477,768 control chromosomes in the GnomAD database, including 74,074 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (12289 hom., cov: 33)
  • Exomes 𝑓: 0.30 (61785 hom.)
• Consequence: TMEM38B NM_018112.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.00200
• Publications: 9 publications found

Genes affected

TMEM38B (HGNC:25535): (transmembrane protein 38B) This gene encodes an intracellular monovalent cation channel that functions in maintenance of intracellular calcium release. Mutations in this gene may be associated with autosomal recessive osteogenesis. [provided by RefSeq, Oct 2012]

TMEM38B Gene-Disease associations (from GenCC):

• osteogenesis imperfecta type 14

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia
• osteogenesis imperfecta type 4

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 9-105694607-A-C is Benign according to our data. Variant chr9-105694607-A-C is described in ClinVar as Benign. ClinVar VariationId is 1271405.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018112.3. 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
	TMEM38B	NM_018112.3	MANE Select	c.-54A>C		5_prime_UTR	Exon 1 of 6	NP_060582.1	Q9NVV0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM38B	ENST00000374692.8	TSL:1 MANE Select	c.-54A>C		5_prime_UTR	Exon 1 of 6	ENSP00000363824.3	Q9NVV0
	TMEM38B	ENST00000956696.1		c.-54A>C		5_prime_UTR	Exon 1 of 7	ENSP00000626755.1
	TMEM38B	ENST00000884631.1		c.-54A>C		5_prime_UTR	Exon 1 of 6	ENSP00000554690.1

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58468 AN: 151600 Hom.: 12258 Cov.: 33

Gnomad AFR AF: 0.540

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.593

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.394

GnomAD4 exome AF: 0.304 AC: 402821 AN: 1326060 Hom.: 61785 Cov.: 19 AF XY: 0.305 AC XY: 203546 AN XY: 666518

African (AFR) AF: 0.534 AC: 16091 AN: 30128

American (AMR) AF: 0.405 AC: 17609 AN: 43498

Ashkenazi Jewish (ASJ) AF: 0.402 AC: 9975 AN: 24806

East Asian (EAS) AF: 0.545 AC: 20824 AN: 38196

South Asian (SAS) AF: 0.361 AC: 29899 AN: 82780

European-Finnish (FIN) AF: 0.288 AC: 15119 AN: 52534

Middle Eastern (MID) AF: 0.464 AC: 2237 AN: 4824

European-Non Finnish (NFE) AF: 0.274 AC: 272388 AN: 993772

Other (OTH) AF: 0.336 AC: 18679 AN: 55522

GnomAD4 genome AF: 0.386 AC: 58546 AN: 151708 Hom.: 12289 Cov.: 33 AF XY: 0.388 AC XY: 28794 AN XY: 74136

African (AFR) AF: 0.541 AC: 22393 AN: 41402

American (AMR) AF: 0.399 AC: 6088 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 1434 AN: 3462

East Asian (EAS) AF: 0.594 AC: 3042 AN: 5124

South Asian (SAS) AF: 0.370 AC: 1786 AN: 4824

European-Finnish (FIN) AF: 0.302 AC: 3172 AN: 10502

Middle Eastern (MID) AF: 0.476 AC: 139 AN: 292

European-Non Finnish (NFE) AF: 0.287 AC: 19432 AN: 67822

Other (OTH) AF: 0.393 AC: 830 AN: 2110

Alfa AF: 0.283 Hom.: 1636

Bravo AF: 0.402

Asia WGS AF: 0.470 AC: 1622 AN: 3458

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.8
DANN	Benign	0.59
PhyloP100		-0.0020
PromoterAI		-0.024	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=300/0	polymorphism (auto)

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: rs2271247; hg19: chr9-108456888; COSMIC: COSV65966907;