11-34494703-T-G

Variant names:

• chr11-34494703-T-G
• rs3781710
• NM_001422.4:c.122-991A>C

Variant summary

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

The NM_001422.4(ELF5):​c.122-991A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 151,968 control chromosomes in the GnomAD database, including 26,901 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 0.59 (26901 hom., cov: 31)
• Consequence: ELF5 NM_001422.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.288
• Publications: 8 publications found

Genes affected

ELF5 (HGNC:3320): (E74 like ETS transcription factor 5) This gene encodes an epithelium-specific ETS family transcription factor. In addition to its role in regulating the later stages of terminal differentiation of keratinocytes, it appears to regulate a number of epithelium-specific genes found in tissues containing glandular epithelium such as salivary gland and prostate. It has very low affinity to DNA due to its negative regulatory domain at the amino terminus. This gene has been implicated as a tumor suppressive transcription factor in breast cancer. [provided by RefSeq, May 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELF5	NM_001422.4	c.122-991A>C		intron_variant	Intron 2 of 6	ENST00000257832.7	NP_001413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELF5	ENST00000257832.7	c.122-991A>C		intron_variant	Intron 2 of 6	1	NM_001422.4	ENSP00000257832.3

Frequencies

GnomAD3 genomes AF: 0.589 AC: 89433 AN: 151850 Hom.: 26880 Cov.: 31

Gnomad AFR AF: 0.493

Gnomad AMI AF: 0.823

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.546

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.744

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.647

Gnomad OTH AF: 0.572

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

GnomAD4 genome AF: 0.589 AC: 89501 AN: 151968 Hom.: 26901 Cov.: 31 AF XY: 0.590 AC XY: 43814 AN XY: 74294

African (AFR) AF: 0.494 AC: 20445 AN: 41420

American (AMR) AF: 0.560 AC: 8558 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.546 AC: 1894 AN: 3470

East Asian (EAS) AF: 0.472 AC: 2435 AN: 5164

South Asian (SAS) AF: 0.462 AC: 2222 AN: 4814

European-Finnish (FIN) AF: 0.744 AC: 7855 AN: 10556

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.647 AC: 43982 AN: 67960

Other (OTH) AF: 0.571 AC: 1203 AN: 2108

Alfa AF: 0.610 Hom.: 20390

Bravo AF: 0.573

Asia WGS AF: 0.478 AC: 1662 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.8
DANN	Benign	0.72
PhyloP100		-0.29
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: rs3781710; hg19: chr11-34516250;