rs4938723

Variant names:

• chr11-111511840-T-C
• rs4938723
• NM_001367975.1:c.-27+341A>G

GermlineCancer (beta)

Variant summary

Our verdict is Benign.

<-10 Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -12 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_Strong

The NM_001367975.1(BTG4):c.-27+341A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.321 (AC=48,754) in the gnomAD database across 152,096 control chromosomes, including 7,984 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.359. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.32 (7984 hom., cov: 32)
• Consequence: BTG4 NM_001367975.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.599
• Publications: 179 publications found

Genes affected

BTG4 (HGNC:13862): (BTG anti-proliferation factor 4) The protein encoded by this gene is a member of the BTG/Tob family. This family has structurally related proteins that appear to have antiproliferative properties. This encoded protein can induce G1 arrest in the cell cycle. [provided by RefSeq, Jul 2008]

BTG4 Gene-Disease associations (from GenCC):

• oocyte maturation defect 8

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics
• female infertility

  Inheritance: AR Classification: MODERATE Submitted by: Franklin by Genoox

MIR34BHG (HGNC:55987): (MIR34B and MIR34C host gene)

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

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

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).
	BA1Stand-alone benign allele frequency (>5%)		GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.3586 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_001367975.1. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTG4	NM_001367975.1	MANE Select	c.-27+341A>G		intron	N/A	NP_001354904.1	A0A8I5KVE8
	BTG4	NM_001367974.1		c.-27+2827A>G		intron	N/A	NP_001354903.1	A0A8I5KVE8
	BTG4	NM_017589.4		c.-27+341A>G		intron	N/A	NP_060059.1	Q9NY30-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTG4	ENST00000692032.1	MANE Select	c.-27+341A>G		intron	N/A	ENSP00000509850.1	A0A8I5KVE8
	BTG4	ENST00000525791.5	TSL:1	c.-27+341A>G		intron	N/A	ENSP00000432018.1	Q9NY30-2
	BTG4	ENST00000689553.1		c.-111+341A>G		intron	N/A	ENSP00000508793.1	A0A8I5KVE8

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 4 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.321	AC:48745	Hom:7981	AN:151978	Cov:32
GnomAD4 genome	AF: 0.321	AC:48754	Hom:7984	AN:152096	Cov:32
TOPMed (Bravo)	AF: 0.316	AC:83748	Hom:13709	AN:264690	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.345	AC:73409	Hom:12885	AN:212492	Cov:
Local & regional cohorts 10 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.348	AC:814	Hom:154	AN:2342	Cov:
ChinaMAP Phase 1	AF: 0.306	AC:	Hom:	AN:	Cov:
Denmark Genome	AF: 0.343	AC:103	Hom:	AN:300	Cov:
GenomeAsia100K	AF: 0.249	AC:864	Hom:	AN:3478	Cov:
Korea4K (4,157 Koreans)	AF: 0.294	AC:2128	Hom:	AN:7232	Cov:
Qatari Genome	AF: 0.307	AC:54	Hom:	AN:176	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.304	AC:37292	Hom:5696	AN:122804	Cov:
Turkish Variome	AF: 0.402	AC:622	Hom:135	AN:1546	Cov:
UK10K	AF: 0.347	AC:2621	Hom:	AN:7562	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 0.303	AC:2719	Hom:419	AN:8960	Cov:

Showing 14 sources

Tested, but no data found:GnomAD4 exomeIf GnomAD4 is missing, the position is probably not covered by the project.

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	2.1
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.3
DANN	Benign	0.72
GPN-Star LLR	N/A	0.30
GPN-Star score	N/A	-0.30
Mutation Taster	N/A	100/0	polymorphism (auto)
PhyloP100	Benign	-0.60
PromoterAI	N/A	0.033	Neutral

Showing 9 of 9 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0
SpliceAI score (max)	Benign	0.0	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4938723;

hg19: chr11-111382565;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar