chr6-96617336-G-A

Variant names:

• chr6-96617336-G-A
• rs11759769
• NM_001322466.2:c.*1564G>A

Variant summary

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

The NM_001322466.2(FHL5):​c.*1564G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 152,114 control chromosomes in the GnomAD database, including 2,724 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 0.18 (2724 hom., cov: 33)
• Consequence: FHL5 NM_001322466.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.195
• Publications: 22 publications found

Genes affected

FHL5 (HGNC:17371): (four and a half LIM domains 5) The protein encoded by this gene is coordinately expressed with activator of cAMP-responsive element modulator (CREM). It is associated with CREM and confers a powerful transcriptional activation function. CREM acts as a transcription factor essential for the differentiation of spermatids into mature spermatozoa. There are multiple polyadenylation sites found in this gene. Polymorphisms in this gene may be associated with susceptibility for migraine headaches. Alternative splicing results in multiple transcript variants encoding the same protein. [provided by RefSeq, Apr 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FHL5	NM_001322466.2	c.*1564G>A		3_prime_UTR_variant	Exon 6 of 6	ENST00000450218.6	NP_001309395.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FHL5	ENST00000450218.6	c.*1564G>A		3_prime_UTR_variant	Exon 6 of 6	5	NM_001322466.2	ENSP00000396390.2

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27485 AN: 151996 Hom.: 2725 Cov.: 33

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.0437

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.207

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

GnomAD4 genome AF: 0.181 AC: 27474 AN: 152114 Hom.: 2724 Cov.: 33 AF XY: 0.179 AC XY: 13294 AN XY: 74352

African (AFR) AF: 0.117 AC: 4850 AN: 41510

American (AMR) AF: 0.179 AC: 2735 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 767 AN: 3468

East Asian (EAS) AF: 0.0438 AC: 227 AN: 5186

South Asian (SAS) AF: 0.179 AC: 862 AN: 4820

European-Finnish (FIN) AF: 0.188 AC: 1984 AN: 10554

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.225 AC: 15310 AN: 67974

Other (OTH) AF: 0.204 AC: 431 AN: 2114

Alfa AF: 0.204 Hom.: 5281

Bravo AF: 0.177

Asia WGS AF: 0.110 AC: 384 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.4
DANN	Benign	0.15
PhyloP100		-0.20

Splicing

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

Other links and lift over

dbSNP: rs11759769; hg19: chr6-97065212;