chr5-73498704-C-A

Variant names:

• chr5-73498704-C-A
• rs1415192584
• NM_001037637.2:c.37C>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001037637.2(BTF3):​c.37C>A​(p.Arg13Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000744 in 1,343,990 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: BTF3 NM_001037637.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.449
• Publications: 0 publications found

Genes affected

BTF3 (HGNC:1125): (basic transcription factor 3) This gene encodes the basic transcription factor 3. This protein forms a stable complex with RNA polymerase IIB and is required for transcriptional initiation. Alternative splicing results in multiple transcript variants encoding different isoforms. This gene has multiple pseudogenes. [provided by RefSeq, Jul 2008]

BTF3-DT (HGNC:55211): (BTF3 divergent transcript)

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.19).
• BP7: Synonymous conserved (PhyloP=0.449 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTF3	NM_001037637.2	c.37C>A	p.Arg13Arg	synonymous_variant	Exon 1 of 6	ENST00000380591.8	NP_001032726.1
BTF3	NM_001393652.1	c.37C>A	p.Arg13Arg	synonymous_variant	Exon 1 of 5		NP_001380581.1
BTF3	NM_001207.5	c.-1+146C>A		intron_variant	Intron 1 of 5		NP_001198.2
BTF3	NM_001393653.1	c.-1+146C>A		intron_variant	Intron 1 of 4		NP_001380582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTF3	ENST00000380591.8	c.37C>A	p.Arg13Arg	synonymous_variant	Exon 1 of 6	1	NM_001037637.2	ENSP00000369965.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.44e-7 AC: 1 AN: 1343990 Hom.: 0 Cov.: 31 AF XY: 0.00000151 AC XY: 1 AN XY: 663434

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 26900

American (AMR) AF: 0.00 AC: 0 AN: 23828

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22470

East Asian (EAS) AF: 0.00 AC: 0 AN: 32614

South Asian (SAS) AF: 0.00 AC: 0 AN: 74960

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38854

Middle Eastern (MID) AF: 0.000193 AC: 1 AN: 5194

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1063542

Other (OTH) AF: 0.00 AC: 0 AN: 55628

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.19
CADD	Benign	16
DANN	Benign	0.92
PhyloP100		0.45
PromoterAI		-0.013	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs1415192584; hg19: chr5-72794529;