3-149054135-A-G

Variant names:

• chr3-149054135-A-G
• rs2034906
• NM_003071.4:c.1473+1168T>C

Variant summary

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

The NM_003071.4(HLTF):​c.1473+1168T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 152,044 control chromosomes in the GnomAD database, including 42,634 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 0.74 (42634 hom., cov: 32)
• Consequence: HLTF NM_003071.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.115
• Publications: 7 publications found

Genes affected

HLTF (HGNC:11099): (helicase like transcription factor) This gene encodes a member of the SWI/SNF family. Members of this family have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein contains a RING finger DNA binding motif. Two transcript variants encoding the same protein have been found for this gene. However, use of an alternative translation start site produces an isoform that is truncated at the N-terminus compared to the full-length protein. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003071.4. 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
	HLTF	NM_003071.4	MANE Select	c.1473+1168T>C		intron	N/A	NP_003062.2
	HLTF	NM_001318935.2		c.1473+1168T>C		intron	N/A	NP_001305864.1
	HLTF	NM_139048.3		c.1473+1168T>C		intron	N/A	NP_620636.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLTF	ENST00000310053.10	TSL:1 MANE Select	c.1473+1168T>C		intron	N/A	ENSP00000308944.5
	HLTF	ENST00000392912.6	TSL:1	c.1473+1168T>C		intron	N/A	ENSP00000376644.2
	HLTF	ENST00000465259.5	TSL:1	c.1470+1168T>C		intron	N/A	ENSP00000420745.1

Frequencies

GnomAD3 genomes AF: 0.745 AC: 113164 AN: 151926 Hom.: 42586 Cov.: 32

Gnomad AFR AF: 0.835

Gnomad AMI AF: 0.761

Gnomad AMR AF: 0.786

Gnomad ASJ AF: 0.829

Gnomad EAS AF: 0.712

Gnomad SAS AF: 0.575

Gnomad FIN AF: 0.690

Gnomad MID AF: 0.834

Gnomad NFE AF: 0.698

Gnomad OTH AF: 0.780

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.745 AC: 113272 AN: 152044 Hom.: 42634 Cov.: 32 AF XY: 0.741 AC XY: 55112 AN XY: 74330

African (AFR) AF: 0.835 AC: 34668 AN: 41494

American (AMR) AF: 0.786 AC: 12012 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.829 AC: 2876 AN: 3470

East Asian (EAS) AF: 0.712 AC: 3682 AN: 5174

South Asian (SAS) AF: 0.575 AC: 2775 AN: 4824

European-Finnish (FIN) AF: 0.690 AC: 7262 AN: 10524

Middle Eastern (MID) AF: 0.839 AC: 245 AN: 292

European-Non Finnish (NFE) AF: 0.698 AC: 47421 AN: 67972

Other (OTH) AF: 0.777 AC: 1637 AN: 2108

Alfa AF: 0.706 Hom.: 19528

Bravo AF: 0.762

Asia WGS AF: 0.673 AC: 2336 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	9.6
DANN	Benign	0.79
PhyloP100		-0.12
Mutation Taster		=100/0	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: rs2034906; hg19: chr3-148771922;